FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma

BACKGROUND Stomach adenocarcinoma(STAD)is one of the main reasons for cancer-related deaths worldwide.This investigation aimed to define the connection between STAD and Cuproptosis-related genes(CRGs).Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper.AIM To explore the identification of potential biomarkers for STAD disease based on cuproptosis.METHODS A predictive model using Gene Ontology(GO),Least Absolute Shrinkage and Selection Operator(LASSO),Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis analyzed gene interconnections,focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD.Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed.The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic,Kaplan-Meier curves,and COX regression analysis.Validation was conducted with datasets GSE26942,GSE54129,and GSE66229.Expression of copper-related differ-entially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas.RESULTS Three significant genes(FDX1,LIAS,MTF1)were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups.These genes were down-regulated in both risk categories.GO and KEGG analyses highlighted their involvement mainly in the electron transport chain.After validating their differential expression,FDX1 emerged as the most accurate diagnostic marker for gastric cancer.Additionally,the RCircos package localized FDX1 on chromosome 11.CONCLUSION Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy,providing new ideas for further scientific research.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma

BACKGROUND Alternative splicing(AS)increases the diversity of mRNA during transcription;it might play a role in alteration of the immune microenvironment,which could influence the development of immunotherapeutic strategies against cancer.AIM To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma(STAD)from the database.The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.METHODS Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model.In STAD,2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions.Furthermore,the network of splicing factors and overallsurvival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.RESULTS An eleven-AS-signature prognostic model(CD44|14986|ES,PPHLN1|21214|AT,RASSF4|11351|ES,KIAA1147|82046|AP,PPP2R5D|76200|ES,LOH12CR1|20507|ES,CDKN3|27569|AP,UBA52|48486|AD,CADPS|65499|AT,SRSF7|53276|RI,and WEE1|14328|AP)was constructed and significantly related to STAD overall survival,immune cells,and cancer-related pathways.The differentially expressed immune-related genes between the high-and low-risk score groups were significantly enriched in cancer-related pathways.CONCLUSION This study provided an AS-related prognostic model,potential mechanisms for AS,and alterations in the immune microenvironment(immune cells,genes,and pathways)for future research in STAD.

Prognostic value of sorting nexin 10 weak expression in stomach adenocarcinoma revealed by weighted gene coexpression network analysis

AIM TO detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma （SA） prognosis.METHODS The Cancer Genome Atlas database was used to obtain RNA sequences as well as complete clinical data of SA and adjacent normal tissues from patients. Weighted gene co-expression network analysis （WGCNA） was used to investigate the meaningful module along with hub genes. Expression of hub genes was analyzed in 362 paraffin-embedded SA biopsy tissues by immunohistochemical staining. Patients were classified into two groups （according to expression of hub genes）： Weak expression and over-expression groups. Correlation of biomarkers with clinicopathological factors indicated patient survival.RESULTS Whole genome expression level screening identified 6,231 differentially expressed genes. Twenty-four co- expressed gene modules were identified using WGCNA. Pearson＇s correlation analysis showed that the tan module was the most relevant to tumor stage （r = 0.24, P = 7 × 10 -6）. In addition, we detected sorting nexin （SNX）10 as the hub gene of the tan module. SNX10 expression was linked to T category （P = 0.042, x2= 8.708）, N category （P = 0.000, x2= 18.778）, TNM stage （P = 0.001, x2 = 16.744） as well as tumor differentiation （P = 0.000,x2= 251.930）. Patients with high SNX10 expression tended to have longer diseasefree survival （DFS; 44.97 mo vs 33.85 mo, P = 0.000） as well as overall survival （OS; 49.95 vs 40.84 mo, P = 0.000） in univariate analysis. Multivariate analysis showed that dismal prognosis could be precisely predicted clinicopathologically using SNX10 [DFS： P = 0.014, hazard ratio （HR） = 0.698, 95% confidence interval （CI）： 0.524-0.930, OS： P = 0.017, HR = 0.704, 95%CI： 0.528-0.940].CONCLUSION This study provides a new technique for screening prognostic biomarkers of SA. Weak expression of SNX10 is linked to poor prognosis, and is a suitable prognostic biomarker of SA.

Comprehensive bioinformatic analysis of mind bomb 1 gene in stomach adenocarcinoma

BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.

Bioinformatics Analysis Revealed Potential Tumor Suppressors (KLF4/CGN), Oncogenes (SHH/LIF) and Biomarkers of Asian Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to identify potential novel oncogenes and tumor suppressor genes, and biomarkers for STAD. 6652 differentially expressed genes were identified between STAD and normal samples based on the transcriptome data analysis of the TCGA and GEO databases. 13 key modules were identified in STAD by WGCNA analysis. 293 potential STAD associated genes were identified from intersection by Venn Diagram. The 293 intersected genes were enriched in cell cortex and infection by GO and KEGG analysis. 10 hub genes were identified from PPI and Cytoscape analyses of the intersected genes. KLF4/CGN low and SHH/LIF high expression were associated with short overall survival of Asian STAD patients. Bioinformatics analysis revealed potential novel tumor suppressors (KLF4/CGN), oncogenes (SHH/LIF) and biomarkers for diagnosis, therapy and prognosis of STAD, specifically for Asian patients.

Progress and current perspectives of diagnosis and treatment of hepatoid adenocarcinoma of the stomach

Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.

Hepatoid adenocarcinoma of the stomach:Thirteen case reports and review of literature

BACKGROUND The aim of the present study was to examine the clinical characteristics of hepatoid adenocarcinoma of the stomach (HAS) and its diagnosis,treatment,and prognosis.CASE SUMMARY A retrospective analysis of 13 HAS cases was performed.The mean age of the 13patients was 66.08 years,and 10 of the 13 patients were male.Prior to treatment,the alpha-fetoprotein levels in the serum were elevated in 7 patients,the tumour was located in the distal or gastric body in 11 patients,and the gastroscopy pathological results showed that 3 patients had poorly differentiated tumours and that 8 patients had moderately/poorly differentiated tumours.Abdominal CT scans showed local stomach wall thickening,and enlarged lymph nodes were visible around the stomach in 8 patients.Of the 13 patients,11 underwent radical surgery.The clinical pathological staging was as follows:Stage Ⅱ in 2 cases;stage Ⅲ in 8 cases;and stage Ⅳ in 1 case.A total of 3 patients were lost to follow-up.Otherwise,as of the last follow-up,3 patients had survived for 56 mo,and the other 7 patients failed to achieve long-term survival (survival period of 1-56 mo).CONCLUSION HAS is a special type of gastric cancer,and the prognosis of HAS has improved compared with past prognoses.Measurement of alpha-fetoprotein,early diagnosis,active surgical treatment,and application of new diagnostic and treatment techniques are conducive to improving the prognosis of HAS.

Liver metastasis from hepatoid adenocarcinoma of the stomach mimicking hepatocellular carcinoma: Dynamic computed tomography findings

AIM: To evaluate the dynamic computed tomography(CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach(HAS) and compared them with hepatocellular carcinoma(HCC).METHODS: Between January 2000 and January 2015, 8 patients with pathologically proven HAS and liver metastases were enrolled. Basic tumor status was evaluated for the primary tumor location and metastatic sites. The CT findings of the liver metastases were analyzed for tumor number and size, presence of tumor necrosis, hemorrhage, venous tumor thrombosis, and dynamic enhancing pattern.RESULTS: The body and antrum were the most common site for primary HAS(n = 7), and observed metastatic sites included the liver(n = 8), lymph nodes(n = 7), peritoneum(n = 4), and lung(n = 2). Most of the liver metastases exhibited tumor necrosis regardless of tumor size. By contrast, tumor hemorrhage was observed only in liver lesions larger than 5 cm(n = 4). Three patterns of venous tumor thrombosis were identified: direct venous invasion by the primary HAS(n = 1), direct venous invasion by the liver metastases(n = 7), and isolated portal vein tumor thrombosis(n = 2). Dynamic CT revealed arterial hyperattenuation and late phase washout in all the liver metastases.CONCLUSION: On dynamic CT, liver metastasis from HAS shared many imaging similarities with HCC. For liver nodules, the presence of isolated portal vein tumor thrombosis and a tendency for tumor necrosis are imaging clues that suggest the diagnosis of HAS.

Hepatoid adenocarcinoma of the stomach: A report of three cases

Hepatoid adenocarcinoma of the stomach (HAS) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. Here, we report on three patients with suspected gastric cancer who were referred to our hospital. Gastrointestinal fiberscopy on the three patients revealed two lesions in the antrum and a third lesion in the gastroesophageal junction. The alpha fetoprotein (AFP) serum levels were markedly elevated in all cases. At the time of diagnosis, two cases were advanced stages with lymph nodes and/or liver metastases. Two patients underwent exploratory laparotomy. A total gastrectomy was performed on the operable lesion, and an expanded gastrectomy was completed in the case with hepatic metastases. Histopathological analysis revealed that the tumors displayed two pathological changes:hepatoid-like foci and adenocarcinomatous. Furthermore, the tumor cells were immunohistochemically positive for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. All three patients received chemotherapy. The follow-up duration ranged from 8-36 mo. Our experience and previous published studies have suggested that HAS is an aggressive type of adenocarcinoma. However, radical surgery and chemotherapy may positively impact clinical outcomes.

STERIGMATOCYSTIN INDUCED ADENOCARCINOMA OF THE LUNG AND ATYPICAL HYPERPLASIA OF GLANDULAR STOMACH IN MICE

Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the lung in 15 of 35 mice (42.9%) and atypical hyperplasia of the glandular stomach in 13 of 35 mice (37.4%). Sterigmatocystin was identified by high performance liquid chromato-graphy (HPLC) and fluorescence spectrophotometry in the extract of Aspergillus-inoculated corn flour. The results suggest that the mycotoxin Sterigmatocystin may play a potential role in carcinogenesis in human.

Gastric hepatoid adenocarcinoma: A computed tomography report of six cases

We describe the computed tomography(CT)imaging findings in six cases(five males and one female;age range 61-78 years;mean age 67.3 years)with histologically proven hepatoid adenocarcinoma of the stomach(HAS).Five of the six patients had elevated serum alpha-fetoprotein levels.The most common type of gross appearance HAS on CT is a polypoid mass(83%,5/6).The most common contrast enhancement pattern was heterogeneous.All six patients had a regional lymphadenopathy larger than 6 mm in its short axis.Liver metastases(n=3)were noted.Venous tumor thrombosis was identified in the portal vein(n=2)of the regions near primary gastric tumors or metastatic masses.Our findings suggest in an elderly,male patients with a large heterogeneous enhancement tumor,the presence of distant metastases,regional lymphadenopathy and characteristically increased serum alphafetoprotein levels indicates a high likelihood of HAS.

Correlation of the expression of gonadotropin releasing hormone and its receptor in human gastric adenocarcinoma cell proliferation and differentiation

AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferation and differentiation.METHODS:GnRH and its receptor and PCNA were detected in 30 gastric adenocarcinoma by immunohistochemical ABC technique. RESULTS:GnRH and its receptor had the same distribution pattern in gastric adenocarcinoma cells.The positive signal was found mainly in cytoplasm.The content of GnRH and its receptor immunoreative product in high differentiatied adenocarcinoma was significantly higher than those of the other two groups and the low differentiatied adenocarcinoma was the lowest(P< 0.05).PCNA positive signal which was found mainly in nucleus was gradually abated along with the raising of the extent of the differentiation.The differences were significant among the three groups(P< 0.05). In human gastric adenocarcinoma,the expression of GnRH and its receptor was negative correlation with the expression of PCNA(r=0.9).CONCLUSION:GnRH might be involved in the regulation of human gastric adenocarcinoma cell proliferation and differentiation.

ARID1A expression in gastric adenocarcinoma:Clinicopathological significance and correlation with DNA mismatch repair status

AIM:To analyze the mismatch repair(MMR)status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.METHODS:We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas.The results were further correlated with clinicopathological variables.RESULTS:The loss of any MMR protein expression,indicative of MMR deficiency,was observed in 38cases(7.8%)and was significantly associated with an older age(68.6±9.2 vs 60.4±11.7,P<0.001),a female sex(55.3%vs 31.3%,P=0.004),an antral location(44.7%vs 25.7%,P=0.021),and a differentiated histology(57.9%vs 39.7%,P=0.023).Abnormal ARID1A expression,including reduced or loss of ARID1A expression,was observed in 109 cases(22.3%)and was significantly correlated with lymphatic invasion(80.7%vs 69.5%,P=0.022)and lymph node metastasis(83.5%vs 73.7%,P=0.042).The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency(47.4%vs 20.2%,P<0.001).A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion,lymph node metastasis,poor prognosis,and MMR deficiency in gastric adenocarcinomas.

Gastric Adenocarcinoma Treatment in Africa: Surgery Alone or Perioperative Chemotherapy?

Aim: Evaluate the impact of MAGIC trial on gastric adenocarcinoma’s management in Africa. Method and methodology: It was about a review of literature on therapeutic aspects of gastric adenocarcinoma in the African area. We have taken a census of 21 articles including 2792 patients published between 1980 and 2013. We have distinguished articles published before 2006 (group 1) from those published after 2006 (group 2) to better understand therapeutic changes after that perioperative chemotherapy has become a standard in gastric adenocarcinoma’s management. Results: Surgery remains in Africa the first and practically the only treatment weapon in gastric adenocarcinoma: 46% to 92% people in the 1st group and 65% to 100% people in the 2nd group underwent surgical procedures. Perioperative chemotherapy takes longer to be part of therapeutic habits (0.18%). Factors related to patients such alteration of general state with a WHO performance status superior to 2 in 72% of cases, the lack of financial accessibility to anticancerous drugs explains partly the non-use of perioperative chemotherapy. This is also due to factors peculiar to our sanitation structures which don’t have enough cancer specialists. So we noticed that MAGIC trial is simply ignored in certain studies. The lack of adoption of perioperative chemotherapy explains with delayed diagnosis the low survival of patients in the African area. Conclusion: MAGIC trial practically has no effect on therapeutic behavior yet comparatively to gastric adenocarcinoma in Africa. The insurance particularly relies on surgery only until now. However, it might enable us to improve gastric adenocarcinoma’s survival rates.

胃肝样腺癌的CT特征

目的分析胃肝样腺癌的临床和CT特征,提高对本病的认识。资料与方法回顾性分析2012年9月—2023年4月苏州大学附属第一医院经病理证实的38例胃肝样腺癌患者的临床病理资料、实验室检查、CT资料,分析病灶大小、形态、密度、边界、强化方式、转移及侵犯等情况,总结其临床及CT特征。结果38例患者中,血清甲胎蛋白水平升高24例,免疫组化甲胎蛋白表达阳性32例。CT表现为胃壁增厚,门静脉期病变最大截面长径2.38~11.95cm,中位数为5.200(3.365,7.215)cm,23例伴溃疡,20例内见坏死,25例周围侵犯,14例出现肝脏转移,5例出现门静脉系统癌栓。结论胃肝样腺癌为罕见肿瘤,血清甲胎蛋白常增高,CT增强检查肿瘤常较大,可见坏死,渐进性或持续强化,易发生转移、侵犯门静脉,认识这些特征有助于提高诊断水平。

^(18)F-FDG PET/CT在胃肝样腺癌诊断中的价值

目的分析胃肝样腺癌的^(18)F-FDG PET/CT显像特征,结合血清AFP水平,两者联合提高对该病认识及诊断准确率。方法选取5例经病理学证实胃肝样腺癌患者的^(18)F-FDG PET/CT检查资料,分析患者的临床表现、原发病灶位置及形态、最大标准摄取值(SUVmax)、肿瘤标志物水平、预后情况。结果原发病灶位于胃窦3例,位于贲门-胃体处2例。5例病灶的SUVmax范围为7.58~23.6,平均值13.8±6.4。5例中位生存期为8个月。结论胃肝样腺癌是一种特殊类型癌,侵袭性强,临床表现无特异性,明确诊断有赖于影像学与病理结合,无肝脏病变时患者血清AFP升高具有重要的诊断提示意义。

胃底腺型胃癌1例并文献复习

目的探讨胃底腺型胃癌(gastric adenocarcinoma of fundic gland type,GA-FG)的临床特征、诊断及鉴别诊断。方法回顾性分析1例GA-FG患者的诊疗经过,并复习相关文献。结果患者为54岁女性,因胃镜检查时发现胃体上部SMT样褪色调病变。该病变表面黏膜光滑,可见扩张的树枝样血管改变;放大内镜技术联合窄带成像技术(ME+NBI)示:病变周边黏膜呈典型蜂窝状结果,病变呈茶褐色,表面微腺管可见融合,腺管开口大小不一,白区不规则,表面微血管不规则;超声胃镜示:可见胃体黏膜层病变,呈中等偏低回声,起源于黏膜层,与黏膜肌层分界不清,黏膜下层完整,大小约0.8 cm×0.5 cm。内镜下切除后病理:胃底腺型腺癌,镜下面积约:0.3 cm×0.3 cm,浸润至黏膜下层(漫润深度约220μm);脉管浸润(-),神经侵犯(-);水平切缘及垂直切缘未见癌细胞;周围黏膜组织慢性炎。免疫组化:MUC6(+);MUC5AC(-);P53无义突变(-);Desmin(示黏膜肌不完整);Syn个别细胞(+);CgA个别细胞(+);CD31及D2-40(脉管内未见癌栓);Ki-67阳性率约10%。结论GA-FG是一种新的组织学类型胃癌,具有独特的临床内镜及病理特征,预后良好,但需要长期随访。

胃腺癌中抗原处理相关转运蛋白1的表达和临床意义

目的探讨胃腺癌(stomach adenocarcinoma,STAD)中抗原处理相关转运蛋白1(transporter associated with antigen processing 1,TAP1)表达与临床病理特征的关系及其预后意义。方法通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库收集TAP1在STAD组织中的mRNA表达水平和患者临床资料。采用GraphPad Prism软件分析TAP1表达与临床病理特征的关系,采用Kaplan-Meier曲线分析其与患者总生存期的关系。采用蛋白质印迹法检测STAD细胞株MKN45和AGS以及人正常胃黏膜上皮细胞株GES-1中TAP1的蛋白表达。收集2020年1月1日至12月31日武汉大学中南医院病理科的STAD组织标本122例和2020年10月1日至12月31日武汉大学中南医院病理科的正常胃切除标本24例,采用免疫组织化学法检测组织中的TAP1表达,分析其与患者临床病理特征的关系。结果TCGA数据库分析和组织标本的免疫组织化学分析均显示,TAP1在STAD组织中较正常胃组织高表达(均P<0.05)。TAP1在STAD细胞株MKN45中的表达较正常胃黏膜上皮细胞株GES-1高(P<0.01),而人STAD细胞株AGS与GES-1中TAP1水平比较,差异无统计学意义(P>0.05)。在STAD组织中,TAP1蛋白表达水平在STAD的Laurén分型方面比较,差异具有统计学意义(P<0.05)。TCGA数据库分析发现,TAP1表达水平随肿瘤组织分级的增加而升高(P<0.05)。TCGA数据库中STAD患者按TAP1表达中位数6.82分为TAP1高表达组和低表达组。TAP1高表达组中位总生存期更长(57.1个月vs 25.1个月,P<0.05)。结论TAP1在STAD组织中高表达,且与Laurén分型和组织分级相关,为预后保护因素,可作为STAD预后的潜在标志物。

CT动态容积灌注成像检出早期胃癌并评估其病理分型

目的 观察CT动态容积灌注(DVPCT)成像检出早期胃癌并鉴别其病理分型的价值。方法 回顾性分析127例经病理证实的早期胃癌患者,根据术前检查方式分为增强CT组(n=67)或DVPCT组(n=60);比较组间一般资料、CT资料,以及DVPCT组内胃印戒细胞癌(SRCC)与胃腺癌的强化程度、门静脉期与延迟期峰值期相及峰值时间;绘制受试者工作特征(ROC)曲线,计算曲线下面积,评估DVPCT时间-密度曲线(TDC)鉴别早期SRCC与腺癌的效能。结果 DVPCT组肿瘤检出率、剂量长度乘积及有效剂量均高于增强CT组(P均<0.05);2组患者年龄、性别、病理分型、肿瘤位置及肿瘤最大径差异均无统计学意义(P均>0.05)。52例(52/60,86.67%)经DVPCT检出早期胃癌的患者中,SRCC 12例、腺癌39例、黏液腺癌1例;其中,早期胃SRCC与早期胃腺癌患者肿瘤强化程度、门静脉期及延迟期峰值期相及峰值时间差异均有统计学意义(P均<0.05)。以峰值时间37.3 s为最佳截断值,DVPCT TDC鉴别早期胃SRCC与早期胃腺癌的敏感度、特异度、阳性预测值、阴性预测值、准确率及曲线下面积分别为83.33%、84.62%、62.50%、94.29%、84.31%及0.895。结论 DVPCT检出早期胃癌效果优于常规增强CT;TDC可有效鉴别早期胃SRCC与早期胃腺癌。