Mapping the landscape of gastric signet ring cell carcinoma:Overcoming hurdles and charting new paths for advancement

BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.

Caveolin-1,E-cadherin and β-catenin in Gastric Carcinoma,Precancerous Tissues and Chronic Non-atrophic Gastritis

Objective： To investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer. Methods： The expressions of caveolin-1, E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase （SP） immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and β-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively. Results： The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues （P〈0.01）. An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues （P〈0.01）. Moreover, low expressions of caveolin-1, E-cadherin and β-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage （P〈0.05）. The positive rates of caveolin-1 and E-cadherin expressions decreased （P〈0.01）, while an abnormal rate of β-catenin expression increased inversely, with the degree of atypical hyperplasia （P〈0.01）. Caveolin-1 expression correlated positively with E-cadherin （r=0.41, P〈0.05）. Caveolin-1 （r=-0.36, P〈0.05） and E-cadherin （r=-0.45, P〈0.05） expressions negatively correlated with abnormal β-catenin expression. Conclusion： These results suggested that dysregulated expressions of caveolin-1, E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.

Disordered beta-catenin expression and E-cadherin/CDH1 promoter methyiation in gastric carcinoma

AIM： TO investigate the distribution of beta-catenin in nuclei or membrane/cytoplasm of gastric carcinoma cells, the relationship between E-cadherin gene methylation and its expression, and the role of beta-catenin and E-cadherin as potential molecular markers in predicting tumor infiltration. METHODS： Twenty-nine cases of gastric carcinoma, classified as diffuse and intestinal variants, were selected for study. Nuclear and cytoplasmic proteins were purified and beta-catenin content was detected by ELISA. DNA methylation of E-cadherin/CDH1 gene promoter was studied by methylation-specific PCR and compaired with E-cadherin expression detected by immunohistochemistry. RESULTS： In 27 cases of gastric carcinoma, the ratio of beta-catenin content between nuclei and membrane/ cytoplasm was correlated with the T-classification （r = 0.392, P = 0.043）. The significance was present between T2 and T3 groups. No correlation was detected between diffuse and intestinal variants in terms of their betacatenin distribution. In 21 cases of diffuse variants of gastric carcinoma, there was a difference in E-cadherin expression between CDH1 gene-methylated group and non-methylated group （29 % vs 71%, P = 0.027）. No correlation between CDH1 gene methylation and T-classification was found, neither was the significance between E-cadherin expression and tumor infiltration grade. CONCLUSION： Comparative analysis of nuclear and membrane/cytoplasmic beta-catenin can predict local tumor infiltration. E-cadherin/CDH1 gene methylation is an important cause for its gene silence in diffuse variant gastric carcinoma. Methylation of CDH1 gene in the absence of E-cadherin is an early event in gastric carcinogenesis.

Expression of E-cadherin in gastric carcinoma and its correlation with lymph node micrometastasis

AIM: To examine the expression of E-cadherin in the primary tumor and to evaluate its relationship with lymph node micrometastasis (LNM).METHODS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H&E staining. Cytokeratin-20 (CK-20)gene marker was used in this assay. The level of E-cadherin expression in the primary tumor was examined by immunochemical technique (EliVisionTM plus).RESULTS: LNM was detected in 77 (12.5%) lymph nodes of 14 patients (46.7%) with gastric carcinoma. The incidence of LNM was significantly higher in the diffuse type (12 of 19 cases, 63.2%) than in the intestinal type of gastric carcinoma (2 of 11 cases, 18.2%, P = 0.026). The incidence of LNM also increased in accordance with the depth of tumor invasion. The loss of expression of E cadherin in primary tumors was found in 14 (46.7) of 30 tumors. The absence of E-cadherin expression was significantly associated with the Lauren classification (P = 0.026), lymph node metastasis (P = 0.011), the grade of differentiation (P = 0.004) and the lymphatic invasion (P = 0.001). Expression of E-cadherin was negative in 10 (71.4%) of the 14 patients with LNM, and in 4 (25%) of the 16 patients without LNM (P = 0.026). CONCLUSION: The current results indicate that the RT PCR assay is useful for the detection of LNM and can significantly increase the detection rate of lymph node metastasis in patients with gastric carcinoma. The Laurenclassification and depth of tumor invasion are significantlyassociated with lymph node micrometastases. Our findings also indicate that E-cadherin may play an important role in determining the growth type and differentiation of gastric carcinoma. The loss of E-cadherin expression may contribute to LNM.

Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas

AIM： To study the role of CDH1/E-cadherin （E-cad） gene alteration profiles including mutation, loss of heterozygosity （LOH）, promoter polymorphism and hypermethylation in mechanisms of CDH1 inactivation in gastric carcinoma （GC）. METHODS： Specimens were collected surgically from 70 patients with GC. Allelotyping PCR and detection of LOH, denaturing high pressure liquid chromatography and DNA sequencing, restriction fragment length polymorphism analysis, methylation specific PCR, and immunohistochemical staining were used. RESULTS： Promoter polymorphism was not a major mechanism of E-cad inactivation. Only one truncating mutation was found in a diffuse type tumor （3%）. Both LOH and promoter hypermethylation were major mechanisms of E-cad inactivation, but interestingly, there was a negative association between the fraction of allelic loss （LOH） in tumors and hypermethylation of CDH1. Therefore LOH and hypermethylation were two different tumorigenic pathways involved in GC. CONCLUSION： Given the findings that somatic mutation was extremely low and the relationship between LOH and hypermethylation was inverse, any two combinations of these three factors cannot fulfill the classical two-hit hypothesis of CDH1 inactivation. Thus, other mechanisms operating at the transcriptional level or at the post-translational level might be required to induce E-cadherin inactivation.

E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

AIM： To examine the role of E-cadherin and betacatenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas （EBV-GCs）. METHODS： We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients＇ prognosis and the expressions of these proteins. RESULTS： Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 950 confidence interval （CI）, 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs （odds ratio = 2.23; 95% CI, 0.97-5.09）, and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs （P = 0.024）. Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis （P 〈 0.001）. Among EBV- GCs, the depth of invasion （P = 0.005）, lymph node metastasis （P = 0.004） and an intestinal type by Lauren classification （hazard ratio = 9.47; 95% CI, 2.67-33.6） were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC （hazard ratio = 0.32; 95% CI, 0.11-0.93）. CONCLUSION： We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma

AIM： To explore the syndrome differentiation in traditional Chinese medicine （TCM） and gene protein expression in gastric carcinoma METHODS： Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin （E-cad） and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS： The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM （P 〈 0.01）. Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups （x^2= 8.999, P 〉 0.05）. CONCLUSION： E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the incoordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.

Clinical significance of expression of proliferating cell nuclear antigen and E-cadherin in gastric carcinoma

AIM to investigate the expression of proliferating cell nuclear antigen(p CNA)and E-cadherin in gastric carcinoma and to analyze their clinical significance.METHODS A total of 146 patients were selected for this study,including 38 patients with intestinal metaplasia,42with dysplasia,and 66 with primary gastric cancer.In addition,40 patients with normal gastric tissues were selected as controls.the expression of p CNA and E-cadherin was detected by immunohistochemistry.Differences in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma were compared.Subjects with normal gastric tissues were assigned to a normal group,while gastric cancer patients were assigned to a gastric cancer group.the difference in p CNA and E-cadherin expression between these two groups was compared.the relationship between expression of p CNA and E-cadherin and clinicopathological features was also explored in gastric cancer patients.furthermore,prognosis-related factors,as well as the expression of p CNA and E-cadherin,were analyzed in patients with gastric cancer to determine the 3-year survival of these patients.RESULTS the difference in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma was statistically significant(p<0.05).During the transition of normal gastric mucosa to gastric cancer,the p CNA labeling index gradually increased,while the E-cadherin labeling index gradually decreased(p<0.05).the p CNA labeling index was significantly higher and the E-cadherin labeling index was significantly lower in gastric cancer than in dysplasia(p<0.05).the expression of p CNA was significantly higher in the gastric cancer group than in the normal group,but E-cadherin was weaker(p<0.05).there was a negative correlation between the expression of p CNA and E-cadherin in gastric carcinoma(r=-0.741,p=0.000).p CNA expression differed significantly between gastric cancer patients with and without lymph node metastasis and between patients at different t stages.E-cadherin expression also differed significantly between gastric cancer patients with and without lymph node metastasis(p<0.05).High t stage and positive p CNA expression were risk factors for the prognosis of patients with gastric cancer(RR>1),while the positive expression of E-cadherin was a protective factor(RR<1).the sensitivity,specificity,and accuracy of p CNA positivity in predicting the 3-year survival of patients with gastric cancer were 93.33%,38.89%,and0.64,respectively;while these values for E-cadherin negativity were 80.0%,41.67%,and 0.59,respectively.When p CNA positivity and E-cadherin negativity were combined,the sensitivity,specificity,and accuracy were66.67%,66.67%,and 0.67,respectively.CONCLUSION Combined detection of p CNA and E-cadherin can improve the accuracy of assessing the prognosis of patients with gastric cancer.

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Helicobacter pylori infection in relation to E-cadherin gene promoter polymorphism and hypermethylation in sporadic gastric carcinomas

AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.METHODS: Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. Hpyloriwas detected by real-time PCR of the cagA gene from non-neoplastic epithelium.E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry.RESULTS: Hpyloriwas found in 57% of patients with GC.H pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs47%, P = 0.02). Hpylori infection was associated with E-cad methylation in nonneoplastic epithelium; however, no significant difference in H pylori was observed between methylated and unmethylated cancerous lesions.CONCLUSION: Patients with the -160C/C genotype might require Hpyloriinfection to promote the inactivation of CDH1, suggesting that Hpylori infection might affect GC in an initial stage because polymorphism is germ line.Mechanism of hypermethylation of CDH1 promoter in GC is complex, and Hpyloriinfection might affect it in an initial stage.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell populations.This paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same lesion.CASE SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the stomach.The lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy specimen.The lesion was excised using segmental gastrectomy.However,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT lymphoma.These two entities were stage I and coexisted in the same lesion.CONCLUSION It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct borders.Surgical resection is effective for these lesions.

Impact of liver metastasis on immunotherapy in gastric carcinoma

The editorial discusses the impact of liver metastasis on immunotherapy efficacy in gastric cancer(GC)patients.Liver metastasis can hinder the effectiveness of immunotherapy by altering the immune microenvironment,leading to systemic loss of T-cells and reduced treatment response.Studies suggest that liver meta-stases serve as a negative baseline factor for immunotherapy efficacy,resulting in poorer progression-free survival and objective response rates.Strategies such as liver-mediated radiotherapy may help improve treatment outcomes by reshaping the liver’s immune microenvironment and reducing T-cell depletion.Understand-ing the complex interplay between liver metastasis and immunotherapy response is crucial for optimising patient care in GC.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma(aGC),it may lead to an adverse prognosis.Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients.AIM To determine the efficacy and safety of cetuximab(CET)combined with the FOLFOX4 regimen(infusional fluorouracil,folinic acid,and oxaliplatin)as firstline therapy for patients with aGC,who received evidence-based care(EBC).METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled.Of these,60 in the research group(RG)received CET+FOLFOX4 as first-line therapy,whereas 57 in the control group(CG)received FOLFOX4.The efficacy[clinical response rate(RR)and disease control rate(DCR)],safety(liver and kidney dysfunction,leukopenia,thrombocytopenia,rash,and diarrhea),serum tumor marker expression[STMs;carbohydrate antigen(CA)19-9,CA72-4,and carcinoembryonic antigen(CEA)],inflammatory indicators[interleukin(IL)-2 and IL-10],and quality of life(QOL)of the two groups were compared.RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG,with an equivalent safety profile between the two groups.RG exhibited notably reduced CA19-9,CA72-4,CEA,and IL-2 levels following treatment,which were lower than the pre-treatment levels and those in the CG.Post-treatment IL-10 was statistically increased in RG,higher than the pre-treatment level and the CG.Moreover,a significantly improved QOL was evident in the RG.CONCLUSION The CET+FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC.It facilitates the suppression of STMs,ameliorates the serum inflammatory microenvironment,and enhances QOL,without increased adverse drug effects.

Combined gastroscopic and laparoscopic resection of gastric metastatic adenosquamous carcinoma from lung: A case report

BACKGROUND Primary lung cancer is the leading cause of cancer-related death worldwide.Common metastatic sites include the brain,liver,bones,and adrenal glands.However,gastric metastases from lung cancer are rare.This case may be the first report of a combined gastroscopic and laparoscopic resection for gastric metasta-tic adenosquamous carcinoma(ASC).CASE SUMMARY We report a case of gastric metastasis from lung cancer.The patient was a 61-year-old Han Chinese female who first attended our hospital complaining of a per-sistent cough,leading to the diagnosis of advanced-stage lung adenocarcinoma.After more than four years of chemotherapy,the patient began to experience epi-gastric pain.Endoscopy was performed,and pathological examination of biopsy specimens confirmed that the gastric lesion was a metastasis from lung cancer.The lesion was successfully resected by combined gastroscopy and laparoscopy.Histopathological examination of the resected gastric specimen revealed ASC.CONCLUSION Gastric metastases from lung cancer are rare.Endoscopy,histological and immunohistochemical staining are useful for diagnosing metastatic lesions.Surgical management may provide extended survival in appropriately selected patients.

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Gastric signet-ring cell carcinoma(GSRCC)is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis.Studies have shown that early GSRCC has a good prognosis,while advanced GSRCC is insensitive to radiotherapy,chemotherapy or immune checkpoint blockade therapy.With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry,more detailed atlas of tumor microenvironment(TME)in GSRCC and its association with prognosis could be investigated extensively.Recently,two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME,manifested as highly immunosuppressive,leading to high immune escape.The TME of advanced GSRCC was enriched for immunosuppressive factors,including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells.In addition,GSRCC was mainly infiltrated by follicular B cells.The increased proportion of SRCC was accompanied by a decrease in mucosaassociated lymphoid tissue-derived B cells and a significant increase in follicular B cells,which may be one of the reasons for the poor prognosis of GSRCC.By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism,more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

Expression of COX-2 in Different Subtypes of Gastric Intestinal Metaplasia and Gastric Carcinoma by Tissue Microarray

Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.

Vascular Endothelial Growth Factor C Expression in Gastric Carcinoma and Its Relationship with Lymph Node Metastasis

Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.

The Relationship between the Expression of p27^(Kip1),p53 and the Infiltration,Metastasis and Prognosis in Gastric Carcinoma

Objective: To study the relationship between the expression of p27Kip1 and p53, and the infiltration, metastasis and prognosis in gastric carcinoma. Methods: The expression of p27Kip1 and p53 at protein level was determined by immunohistochemical assay (two-step method) in 100 cases of gastric carcinoma. Results: Of the 100 cases, the positive rate of p27Kip1 and p53 expressions were 44% and 49%, respectively. In the group of gastric carcinomas with deep infiltration (infiltration group), lymph nodes metastasis group (metastasis group) and death-within-5-years group (death group), the expression of p27Kip1 was statistically lower (_P<0.05). In the metastasis group and death group, the expression of p53 was significantly higher (P<0.05). The results of the monovariate analysis revealed that the 5-year survival rate of the high p27Kip1 expression group was 70.59%, which is higher than those of the low p27Kip1 expression group (54.55%) and the negative experession group (26%). The 5-year survival rate of the high p53 expression group was 19.23%, which was lower than those of the p53 low expression group (43.75%) and the negative group (53.19%). Cox multivariate analysis showed that p27Kip1, like p53, was an independent prognostic index. But p27Klpl protein expression was a stronger independent survival predictor (RR=3.06) than p53 expression (RR=2.33). Conclusion: The low expression of p27Kip1 and the high expression of p53 reflected the more frequent invasion and metastasis, which resulted in the reduced survival of patients. As an independent markers of the gastric carcinoma, the expression of p27Kip1 is more useful than that of p53 in the prognosis prediction of gastric carcinoma.