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World Journal of Gastroenterology 2005年第6期11卷 875-879页

作者： Li-FenYu YingCheng Min-MinQiao Yong-PingZhang Yun-LinWu DepartmentofGastroenterology RuijinHospitalofShanghaiSecondMedicalUniversityShanghai200025China

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.

关键词： stomach adenocarcinoma Vascular endothelial growth factor STAT3 protein Antineoplastic Drug Resistance

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

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World Journal of Gastroenterology 2018年第43期24卷 4906-4919页

作者： Jun Zhang Yue Wu Hao-Yi Jin Shuai Guo Zhe Dong Zhi-Chao Zheng Yue Wang Yan Zhao Department of Gastric Cancer Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University) Department of Emergency Sheng Jing Hospital of China Medical University Pancreatic and Thyroid Surgery Department Sheng Jing Hospital of China Medical University

AIM TO detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma （SA） *** 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 *** 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.

关键词： stomach adenocarcinoma The Cancer Genome Atlas Weighted gene co-expression network analysis Sorting nexin 10 Clinicopathological pre-dictors Diseasefree survival Overall survival

Comprehensive bioinformatic analysis of mind bomb 1 gene in stomach adenocarcinoma

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World Journal of Gastrointestinal Oncology 2023年第7期15卷 1295-1310页

作者： Di Wang Qi-Hong Wang Ting Luo Wen Jia Jing Wang Department of Digestive Endoscopy The General Hospital of Northern Theater CommandShenyang 110840Liaoning ProvinceChina Postgraduate College China Medical UniversityShenyang 110840Liaoning ProvinceChina

BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling *** 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 ***,studies on the role of MIB1 in STAD are ***,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number *** To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of *** 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 *** Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal *** a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was ***-Meier plotter was used to determine the effect of MIB1 expression on *** 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 *** was used to construct protein-protein interaction networks related to the MIB1 *** 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 *** 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 upregul

关键词： stomach adenocarcinoma Mind bomb 1 Mutation Prognosis Biomarker Immune infiltration

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

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World Journal of Gastroenterology 2021年第21期27卷 2871-2894页

作者： Zai-Sheng Ye Miao Zheng Qin-Ying Liu Yi Zeng Sheng-Hong Wei Yi Wang Zhi-Tao Lin Chen Shu Qiu-Hong Zheng Lu-Chuan Chen Department of Gastrointestinal Surgical Oncology Fujian Cancer Hospital&Fujian Medical University Cancer HospitalFuzhou 350014Fujian ProvinceChina Department of Clinical Laboratory Fujian Maternity and Child Health HospitalAffiliated Hospital of Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Fujian Provincial Key Laboratory of Tumor Biotherapy Fujian Cancer Hospital&Fujian Medical University Cancer HospitalFuzhou 350014Fujian ProvinceChina

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 *** To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma(STAD)from the *** overall survival data associated with AS events were used to construct a signature prognostic model for *** Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic *** STAD,2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular ***,the network of splicing factors and overallsurvival-associated AS events indicated potential regulatory mechanisms underlying the AS events in *** 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 *** differentially expressed immune-related genes between the high-and low-risk score groups were significantly enriched in cancer-related *** 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.

关键词： stomach adenocarcinoma Alternative splicing Tumor microenvironment Immune-related genes and pathways

Reduced Expression and Genetic Alterations of ING4 in Human stomach Adencarcinoma

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Reduced Expression and Genetic Alterations of ING4 in Human ...

Reduced expression and genetic alterations of ING4 in human stomach adencarcinoma

中国遗传学会“发育、遗传和疾病”研讨会

作者： Ming Li~1 Yan Jin~1 Changlong Guo~1 Jing Bai~1 Feng Chen~1 Songbin Fu~(1,2) 1.Laboratory of Medical Genetics,Harbin Medical University,Harbin,150081,China 2.Bio-pharmaceutical Key Laboratory of Heilongjiang Province,Harbin,150081,China

ING4 is a member oflNG gene family and harbors the PHD domain and NLS ***4 is reported to interact with tumor suppressor p53 and found to be involved in various biological activities, including cell cycle arrest,regulation of gene transcription,DNA repair and apoptosis,ING41 is located in nucleus whereas other three variants are located in *** clarify the role of ING4 in human stomach adencarcinoma,we first compared ING4 expression in four human gastric adenocarcinoma cell lines by RT-PCR and Real-time ***/NG4 mRNA level was found in all cell lines,while there is lower ING4 expression found in differentiated cell ***,fourty samples of human stomach adenocarcinoma tissues and matched no-tumor tissues were investigated using RT-PCR and Real-time PCR. ING4 expression level is significantly decreased in stomach adenocarcinoma tissues（P＜0.05）and markedly related to gender and infiltration（P＜0.05）.Then,Expression of ING4 is analyzed among other fourty human stomach adenocarcinoma samples without matched normal tissues and fourty human stomach adenocarcinoma with matched normal tissues,through tissue microarray analysis ING4 expression was found to locate in the nucleus and cytoplasm,especially and interestingly in the parietal ceil,while expression of ING4 is stronger than cytoplasmic *** expression of ING4 was reduced greatly in stomach adenocarcinoma tissues compared with normal stomach tissues（P＜0.01）,but it has no significant relationship with the clinicopathologicai parameters in patients of stomach *** last,we checked mutations in four human gastric adenocarcinoma cell lines and nine random tumor samples using clone sequence,when we found complete and correct ORF sequences of/NG41,/NG42 and ING44, and various mutations in splice variants ING41 and/NG42 as *** these findings suggest that the inhabitation of ING4 gene expression and mutations of ING4 may be involved in the initiation and proceeding of stomach a

关键词： stomach adenocarcinoma Anti-oncogene ING4

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Reduced expression and genetic alterations of ING4 in human ...

Reduced Expression and Aberrant Splicing of ING4 in Human stomach Adencarcinoma

中国遗传学会第八次代表大会暨学术讨论会

作者：李明傅松滨 Laboratory of Medical Genetics Harbin Medical University Bio-pharmaceutical Key Laboratory of Heilongjiang Province

As a member of ING gene family which harbor the PHD domain and NLS domain,ING4 was reported to interact with tumor suppressor p53 and found to be involved in various biological activities,including cell cycle arrest,regulation of gene transcription,DNA repair and apoptosis. ING41 was located in nucleus whereas other three variants were located in *** clarify the role of ING4 in human stomach adencarcinoma,we first compared ING4 expression in four human gastric adenocarcinoma cell lines by RT-PCR and Real-time *** ING4 mRNA level was found in all cell lines,while there was lower ING4 expression found in poorly differentiated cell ***,forty samples of human stomach adenocarcinoma tissues and matched no-tumor tissues were investigated using RT-PCR and Real-time ***4 expression level was significantly decreased in stomach adenocarcinoma tissues(Pstomach adenocarcinoma samples without matched normal tissues and forty human stomach adenocarcinoma samples with matched normal tissues through tissue microarray *** results indicated that ING4 was located in the nucleus and cytoplasm,especially and interestingly in the parietal *** expression of ING4 was reduced greatly in stomach adenocarcinoma tissues compared with normal stomach tissues(Padenocarcinoma cell lines and nine random tumor samples using clone *** data demonstrated complete and correct ORF sequences of ING41,ING42 and ING44,and various mutations in splice variants ING41 and ING42 as *** these findings suggested that the inhibition of ING4 gene expression and mutations of ING4 might be involved in the initiation and proceeding of stomach adenocarcinoma.

关键词： stomach adenocarcinoma anti-oncogene ING4 expression mutation

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Reduced Expression and Aberrant Splicing of ING4 in Human St...

LINC01614 expression in gastric cancer and its prognostic value based on bioinformatics analyses

第八次全国医学遗传学学术会议(中华医学会2009年医学遗传学年会)

作者： LI Ming,JIN Yan,SUN Wen-jing YU Yang~1,BAI Jing~1,CHEN Feng~1,FU Song-bin~(1,2)(1.Laboratory of Medical Genetics,Harbin Medical University,Harbin 150081,China 2.Bio-pharmaceutical Key Laboratory of Heilongjiang Province,Harbin 150081,China)

As a member of ING gene family which harbor the PHD domain and NLS domain,ING4 was reported to interact with tumor suppressor p53 and found to be involved in various biological activities,including cell cycle arrest,regulation of gene transcription, DNA repair and ***41 was located in nucleus whereas other three variants were located in *** clarify the role of ING4 in human stomach adencarcinoma,we first compared ING4 expression in four human gastric adenocarcinoma cell lines by RT-PCR and Real-time *** ING4 mRNA level was found in all cell lines,while there was lower ING4 expression found in poorly differentiated cell ***,forty samples of human stomach adenocarcinoma tissues and matched no-tumor tissues were investigated using RT-PCR and Real-time ***4 expression level was significantly decreased in stomach adenocarcinoma tissues(Pstomach adenocarcinoma samples without matched normal tissues and forty human stomach adenocarcinoma samples with matched normal tissues through tissue microarray *** results indicated that ING4 was located in the nucleus and cytoplasm,especially and interestingly in the parietal *** expression of ING4 was reduced greatly in stomach adenocarcinoma tissues compared with normal stomach tissues(Padenocarcinoma cell lines and nine random tumor samples using clone *** data demonstrated complete and correct ORF sequences of ING41,ING42 and ING44,and aberrant splicing based on ING41 and ING42 as well. All these findings suggested that the inhibition of ING4 gene expression and mutations of ING4 might be involved in the initiation and proceeding of stomach adenocarcinoma.

关键词： stomach adenocarcinoma Anti-oncogene ING4 Expression Variant

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Journal of Hainan Medical University 2020年第10期26卷 42-46页

作者： Hui-Jie Wu Jing-Yuan Zhou Song-Da Chen Ling-Yu Zhu Jia-Hao Liang Ai-QunLiu Department of Endoscopy Center Guangxi Medical University Cancer HospitalNanningGuangxi530021 Department of Hepatobiliary Surgery Guangxi Medical University Cancer HospitalNanningGuangxi530021

Objective:To identify the potential role and prognostic value of LINC01614 in gastric cancer. Methods: qRT-PCR was applied to analyze the LINC01614 expression in gastric cancer tissue and paired adjacent normal tissue, and gastric cell line. And the RNA-Seq data downloaded from the TCGA and GEO database was employed to analyze and validate the LINC01614 expression in gastric cancer tissue and adjacent normal tissue. And the analyses of relationship between LINC01614 expression level and clinical features was done to clarify the role of LINC01614 in gastric cancer. The survival analysis was used to identify the prognostic value of LINC01614. And the pathways that LINC01614 may enroll was ***: The qRT-PCR showed that LINC01614 was increased in gastric cancer tissue and gastric cancer cell line (P < 0.005). And the expression of LINC01614 was significantly different in cancer tissue and adjacent normal tissue according to datasets analyses (P < 0.001). And it was found that LINC01614 expression was significantly correlated with histologic grade and residual tumor (P = 0.0177 and 0.0218, respectively). Survival analysis indicated that low expression of LINC01614 patients have longer overall survival than high expression one (HR = 1.520, 95% CI: 1.094 ~ 2.110). After all, enriched pathways showed that LINC01614 may act in carcinogenesis through various ***: LINC01614 is high expressed in gastric cancer and high expression of LINC01614 is related to poor prognosis. LINC01614 may be a potential prognostic biomarker for gastric cancer.

关键词： stomach adenocarcinoma LINC01614 RNA Long Noncoding Bioinformatics