BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been publishe...BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.展开更多
BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to patho...BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.展开更多
Objective: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). Methods: Clinicopathologic and prognostic ...Objective: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). Methods: Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise). Results: A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P〈0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P〉0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach (P〈0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions: While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.展开更多
BACKGROUND Metastatic skin cancers are relatively rare dermatological malignancies.They usually present as nodules,erythematous lesions,scar-like lesions or other lesion types.Signet-ring cell carcinoma(SRCC)is an unc...BACKGROUND Metastatic skin cancers are relatively rare dermatological malignancies.They usually present as nodules,erythematous lesions,scar-like lesions or other lesion types.Signet-ring cell carcinoma(SRCC)is an uncommon histological type of gastric cancer that usually behaves aggressively and has a poor prognosis.Skin metastasis may be the first sign of clinically silent visceral cancer or recurrence of an internal malignancy.CASE SUMMARY Herein we report on the case of a 55-year-old man with edema of a lower extremity as the primary symptom which progressed from local to generalized pitting edema in the year following skin involvement.Pathological evidence from gastroscopic specimens and subcutaneous tissue biopsy showed typical signetring cells and gland-like structures.Consistently,immunohistochemical analysis revealed positive pan-cytokeratin expression in tumor cells.A diagnosis of gastric SRCC with skin metastasis was established.Moreover,lymphoscintigraphy showed an obvious accumulation of radiotracer on the anterior and posterior sides of the right leg which indicated lymphedema.We reviewed the relevant literature on subcutaneous metastases of gastric SRCC.CONCLUSION This rare case emphasizes the importance of physical examination as it may help elucidate the etiology of edema.展开更多
We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to no...We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to normal levels within 24 h after radical gastrectomy and Billroth II anastomosis.The patient recovered well after the surgery and no abnormalities were found during the regular follow-ups.Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic;moreover,cases of solid malignant tumors with eosinophilia are uncommon.To our knowledge,this is the first reported case of paraneoplastic eosinophilia in a patient with gastric carcinoma.We considered eosinophilia as a manifestation of a paraneoplastic syndrome,which can be the first clinical manifestation of a malignancy.展开更多
While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gas...While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.展开更多
A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. Th...A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.展开更多
Signet-ring cell carcinoma(SRCC) of ampulla of Vater is extremely uncommon,and less than 15 cases have been reported so far in literature.It mainly occurs in elderly people(median age 57 years).We report a rare case o...Signet-ring cell carcinoma(SRCC) of ampulla of Vater is extremely uncommon,and less than 15 cases have been reported so far in literature.It mainly occurs in elderly people(median age 57 years).We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater,discovered by the contrast-enhanced ultrasound(CEUS).Histopathological examination showed prominent signet-ring features.We also describe the imaging features of SRCC of ampulla of Vater in CEUS.展开更多
AIM:To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS:In situ hybridiza...AIM:To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1). BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and-23 of Rb, 5' flanking region of IL-2 and clotting factor Ⅸ genes.CONCLUSION:GCRG123, an active member of the L1 family, was up-regulated in human gastric signet-ring cell carcinoma.展开更多
Objective: To analyze the clinicopathologic features of breast signet-ring cell carcinoma (SRCC) presenting with genital tract metastasis. Methods: A 54-year-old woman presented with metrorrhagia was described and the...Objective: To analyze the clinicopathologic features of breast signet-ring cell carcinoma (SRCC) presenting with genital tract metastasis. Methods: A 54-year-old woman presented with metrorrhagia was described and the immunostaining was performed. Results: Histologically, signet ring cells (SRCs) scattered in the stroma of endometrium and cervix, bilateral fallopian tubes, ovaries and left breast. Immunohistochemistry of these SRCs showed strong reactive for cytokertin 7, CEA, GCDFP-15, and weak reactive for CA125 and negative for cytokertin 20. All these information confirmed the breast origin of SRCC. Conclusion: Primary breast SRCC is extremely rare with metrorrhagia as its first symptom. Gynecologist and pathologist should be aware of this possibility when metrorrhagia is the only symptom. Immunohistochemistry can help differentiate the origin of SRCC.展开更多
We presented an unusual case with coexistence of carcinoid, signet-ring cell carcinoma (SRC) and heterotopic pancreatic tissue in stomach. Gastroscopic examination of this 63-year-old male patient showed multiple prot...We presented an unusual case with coexistence of carcinoid, signet-ring cell carcinoma (SRC) and heterotopic pancreatic tissue in stomach. Gastroscopic examination of this 63-year-old male patient showed multiple protrusions in gastric corpus near the greater curvature, identified by subsequent biopsy as carcinoid. Distal subtotal gastrectomy was performed. Histological and immunohistochemical examinations showed a carcinoid tumor in gastric corpus near the greater curvature, an intramucosal SRC at the lesser curvature of corpus and heterotopic pancreatic tissue in muscularis propria of the antrum at the lesser curvature with hyperplasia of peripheral endocrine cells producing multiple pancreatic hormones. We reviewed the literatures on clinicopathological characteristics and the differential diagnosis of the above three abnormalities, and concluded that the carcinoid in corpus near the greater curvature and SRC in the lesser curvature are independent lesions; the foci of endocrine cells in the muscularis propria and serosa are hyperplastic lesions from the heterotopic pancreatic tissue, rather than dissemination of carcinoid in corpus.展开更多
BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round...BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round or oval,and the nuclear deviations give the cells a signet ring-like appearance.SRCC often originates in the gastrointestinal tract,especially in the stomach.However,primary SRCC of the extrahepatic bile duct is extremely rare.Therefore,little is known about its epidemiology,treatment,and prognosis.CASE SUMMARY An 82-year-old female was admitted with abdominal pain,jaundice,and skin pruritus for 2 mo.She had no specific family history.Physical examination presented normal vital signs,icteric sclera,visible jaundice,and mild tenderness in the right upper abdominal quadrant.Tumor-related cell markers were within normal values.Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct,strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver.In addition,the lymph nodes in the hepatic hilum area,the pancreatic head area,and around the abdominal aorta were enlarged.Thus,a preoperative diagnosis of cholangiocarcinoma was established.To alleviate jaundice and prolong the overall survival,percutaneous transhepatic cholangiopancreatic drainage(PTCD)was performed.During the operation,segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed.Furthermore,a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion.The pathological diagnosis of the biopsy was SRCC.Finally,a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic,PTCD,and pathological characteristics.The tumor was diagnosed as T3N1M1 stage IV.Despite our aggressive approach,the patient died of liver failure after 1 mo.CONCLUSION This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date.展开更多
Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in earl...Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC.Therefore,the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients.In recent years,technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients.Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection(ESD),indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation.This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.展开更多
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate...Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.展开更多
As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major h...As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.展开更多
MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like ot...MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition ...Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.展开更多
Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnosti...Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.展开更多
文摘BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.
基金National Natural Science Foundation of China,No.82200625 and No.82100595Youth Talent Development Program,No.YNRCQN0313+2 种基金Young Scholar Fostering Fund of the First Affiliated Hospital of Nanjing Medical University,No.PY2021023Top Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZBJ051Natural Science Foundation of Jiangsu Province,China,No.BK20210958.
文摘BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.
文摘Objective: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). Methods: Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise). Results: A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P〈0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P〉0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach (P〈0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions: While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.
基金The National Nature Science Foundation of China,No.81900363.
文摘BACKGROUND Metastatic skin cancers are relatively rare dermatological malignancies.They usually present as nodules,erythematous lesions,scar-like lesions or other lesion types.Signet-ring cell carcinoma(SRCC)is an uncommon histological type of gastric cancer that usually behaves aggressively and has a poor prognosis.Skin metastasis may be the first sign of clinically silent visceral cancer or recurrence of an internal malignancy.CASE SUMMARY Herein we report on the case of a 55-year-old man with edema of a lower extremity as the primary symptom which progressed from local to generalized pitting edema in the year following skin involvement.Pathological evidence from gastroscopic specimens and subcutaneous tissue biopsy showed typical signetring cells and gland-like structures.Consistently,immunohistochemical analysis revealed positive pan-cytokeratin expression in tumor cells.A diagnosis of gastric SRCC with skin metastasis was established.Moreover,lymphoscintigraphy showed an obvious accumulation of radiotracer on the anterior and posterior sides of the right leg which indicated lymphedema.We reviewed the relevant literature on subcutaneous metastases of gastric SRCC.CONCLUSION This rare case emphasizes the importance of physical examination as it may help elucidate the etiology of edema.
文摘We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to normal levels within 24 h after radical gastrectomy and Billroth II anastomosis.The patient recovered well after the surgery and no abnormalities were found during the regular follow-ups.Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic;moreover,cases of solid malignant tumors with eosinophilia are uncommon.To our knowledge,this is the first reported case of paraneoplastic eosinophilia in a patient with gastric carcinoma.We considered eosinophilia as a manifestation of a paraneoplastic syndrome,which can be the first clinical manifestation of a malignancy.
文摘While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.
文摘A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.
基金Supported by The Educational Fund of Liaoning Province,No.2008795
文摘Signet-ring cell carcinoma(SRCC) of ampulla of Vater is extremely uncommon,and less than 15 cases have been reported so far in literature.It mainly occurs in elderly people(median age 57 years).We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater,discovered by the contrast-enhanced ultrasound(CEUS).Histopathological examination showed prominent signet-ring features.We also describe the imaging features of SRCC of ampulla of Vater in CEUS.
基金the Key Project from the 10th Five-year Plan of Chinese PLA, No. 01Z035International Cooperation Project from the 11th Five-year Plan of Chinese PLA, No. 06H044
文摘AIM:To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1). BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and-23 of Rb, 5' flanking region of IL-2 and clotting factor Ⅸ genes.CONCLUSION:GCRG123, an active member of the L1 family, was up-regulated in human gastric signet-ring cell carcinoma.
文摘Objective: To analyze the clinicopathologic features of breast signet-ring cell carcinoma (SRCC) presenting with genital tract metastasis. Methods: A 54-year-old woman presented with metrorrhagia was described and the immunostaining was performed. Results: Histologically, signet ring cells (SRCs) scattered in the stroma of endometrium and cervix, bilateral fallopian tubes, ovaries and left breast. Immunohistochemistry of these SRCs showed strong reactive for cytokertin 7, CEA, GCDFP-15, and weak reactive for CA125 and negative for cytokertin 20. All these information confirmed the breast origin of SRCC. Conclusion: Primary breast SRCC is extremely rare with metrorrhagia as its first symptom. Gynecologist and pathologist should be aware of this possibility when metrorrhagia is the only symptom. Immunohistochemistry can help differentiate the origin of SRCC.
文摘We presented an unusual case with coexistence of carcinoid, signet-ring cell carcinoma (SRC) and heterotopic pancreatic tissue in stomach. Gastroscopic examination of this 63-year-old male patient showed multiple protrusions in gastric corpus near the greater curvature, identified by subsequent biopsy as carcinoid. Distal subtotal gastrectomy was performed. Histological and immunohistochemical examinations showed a carcinoid tumor in gastric corpus near the greater curvature, an intramucosal SRC at the lesser curvature of corpus and heterotopic pancreatic tissue in muscularis propria of the antrum at the lesser curvature with hyperplasia of peripheral endocrine cells producing multiple pancreatic hormones. We reviewed the literatures on clinicopathological characteristics and the differential diagnosis of the above three abnormalities, and concluded that the carcinoid in corpus near the greater curvature and SRC in the lesser curvature are independent lesions; the foci of endocrine cells in the muscularis propria and serosa are hyperplastic lesions from the heterotopic pancreatic tissue, rather than dissemination of carcinoid in corpus.
基金Supported by the Zunyi City Science and Technology Department,No.HZ-2021-44.
文摘BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round or oval,and the nuclear deviations give the cells a signet ring-like appearance.SRCC often originates in the gastrointestinal tract,especially in the stomach.However,primary SRCC of the extrahepatic bile duct is extremely rare.Therefore,little is known about its epidemiology,treatment,and prognosis.CASE SUMMARY An 82-year-old female was admitted with abdominal pain,jaundice,and skin pruritus for 2 mo.She had no specific family history.Physical examination presented normal vital signs,icteric sclera,visible jaundice,and mild tenderness in the right upper abdominal quadrant.Tumor-related cell markers were within normal values.Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct,strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver.In addition,the lymph nodes in the hepatic hilum area,the pancreatic head area,and around the abdominal aorta were enlarged.Thus,a preoperative diagnosis of cholangiocarcinoma was established.To alleviate jaundice and prolong the overall survival,percutaneous transhepatic cholangiopancreatic drainage(PTCD)was performed.During the operation,segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed.Furthermore,a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion.The pathological diagnosis of the biopsy was SRCC.Finally,a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic,PTCD,and pathological characteristics.The tumor was diagnosed as T3N1M1 stage IV.Despite our aggressive approach,the patient died of liver failure after 1 mo.CONCLUSION This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date.
文摘Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC.Therefore,the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients.In recent years,technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients.Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection(ESD),indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation.This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.
文摘MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
基金funded by the GRRC Program of Gyeonggi province[GRRC-KyungHee2023(B01)],Republic of Korea.
文摘Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.
基金This study was supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)National Key Research and Development Program of China(2021YFC2301801).
文摘Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.