Achaete Scute同源物2在消化系统肿瘤的表达及其临床意义  

Expression of achaete scute homolog 2 in gastrointestinal tumor and its clinical significance

作　　者：汤守元[1] 姜进平[1] 肖俊[2] 肖勇[2] 张万里[2] Tang Shouyuan;Jiang Jinping;Xiao Jun;Xiao Yong;Zhang Wanli(Department of Gastrointestinal and Anorectal Surgery,Huangshi Central Hospital(Affiliated Hospital of Hubei Institute of Technology),Hubei Medical Group,Huangshi 435000,China;Department of Digestive Oncology,Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]鄂东医疗集团黄石市中心医院(湖北理工学院附属医院)胃肠肛肠外科,黄石435000 [2]华中科技大学同济医学院附属协和医院肿瘤中心消化肿瘤外科,武汉430022

出　　处：《中华实验外科杂志》2022年第5期946-948,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨Achaete Scute同源物2(ASCL2)基因在消化系统肿瘤中的表达及临床意义。方法通过检索基因表达谱数据动态分析(GEPIA)数据库2017年1月至2021年1月筛选出胃癌与结直肠癌均显著变化的ASCL2基因。通过肿瘤免疫估计资源(TIMER)数据库分析ASCL2在各类肿瘤中相对于正常组织的表达水平。利用GEPIA数据库评估ASCL2对消化系统肿瘤临床预后的影响,并通过TIMER数据库研究了ASCL2与癌细胞免疫浸润的相关性。通过cBioportal网站对ASCL2共表达的错配修复基因进行相关性分析。结果神经肽S受体1(NPSR1)、棕榈油酰蛋白羧酸酯酶(NOTUM)、RP11-400N13.2及ASCL2是胃癌、结肠癌与直肠癌共有的与正常组织比较表达差异最显著的4个基因。ASCL2在结肠腺癌、食管腺癌、直肠腺癌及胃腺癌等多数肿瘤中显著高于癌旁组织(0.61±0.03、0.56±0.02、0.67±0.04、0.59±0.03比0.14±0.01),差异有统计学意义(P<0.05)。ASCL2高表达的食管腺癌患者预后差[总生存期:风险比(HR)=1.6,P<0.05;无病生存期:HR=1.6,P<0.05]。cBioportal数据库分析结果显示ASCL2基因表达与错配修复基因MLH1(rs=0.17,P<0.05)和PMS2(rs=0.30,P<0.05)的表达均呈正相关。ASCL2表达与结直肠腺癌肿瘤纯度呈正相关(r=0.237,P<0.05),与结肠腺癌中B细胞(r=-0.159,P<0.05)、CD8+T细胞(r=-0.468,P<0.05)、巨噬细胞(r=-0.115,P<0.05)、中性粒细胞(r=-0.340,P<0.05)和树突状细胞(r=-0.351,P<0.05)的浸润水平呈负相关,在直肠腺癌中与肿瘤纯度呈正相关(r=0.260,P<0.05),与CD8+T细胞(r=-0.431,P<0.05)、中性粒细胞(r=-0.305,P<0.05)和树突状细胞(r=-0.186,P<0.05)的浸润水平呈负相关。结论ASCL2在消化系统肿瘤组织中呈高表达状态且抑制消化系统肿瘤患者机体免疫,与其预后密切相关。Objective The expression and clinical significance of achaete scute homolog 2(ASCL2)gene in gastrointestinal cancer were analyzed by data mining of Oncomine,tumor immune estimation resource(TIMER),cBioportal and gene expression profiling interactive analysis(GEPIA).Methods By searching GEPIA database from January 2017 to January 2021,ASCL2 gene with significant changes in both gastric and colorectal cancer was screened.The expression level of ASCL2 in various tumors was analyzed by the TIMER database.GEPIA database was used to evaluate the effect of ASCL2 on the clinical prognosis of gastrointestinal cancer,and the correlation between ASCL2 and cancer cell immune invasion was studied by the TIMER database.In addition,the correlation of mismatch repair genes co-expressed by ASCL2 was analyzed by cBioportal.Results NPSRL,NOTUM,RP11-400N13.2 and ASCL2 were the four genes with the most significant difference in gastric cancer,colon cancer and rectal cancer.ASCL2 was significantly higher in most tumors such as colon adenocarcinoma,esophageal adenocarcinoma,rectal adenocarcinoma and gastric adenocarcinoma(0.61±0.03,0.56±0.02,0.67±0.04,0.59±0.03 vs.0.14±0.01,respectively)with statistically significances(all P<0.05).Patients with esophageal adenocarcinoma with high ASCL2 expression had poor prognosis[total survival:hazard ratio(HR)=1.6,P<0.05;disease-free survival:HR=1.6,P<0.05].The expression of ASCL2 gene was significantly correlated with the expression of MLH1(rs=0.17,P<0.05)and PMS2(rs=0.30,P<0.05).The expression of ASCL2 was positively correlated with tumor purity in colorectal adenocarcinoma(r=0.237,P<0.05),and negatively correlated with the infiltration of B cells(r=-0.159,P<0.05),CD8+T cells(r=-0.468,P<0.05),macrophages(r=-0.115,P<0.05),neutrophils(r=-0.34,P<0.05)and dendritic cells(r=-0.351,P<0.05)in colorectal adenocarcinoma.And there was a negative association with CD8+T cell,neutrophil and dendritic cell infiltration in rectal adenocarcinoma.Conclusion ASCL2 is highly expressed in gastrointestinal tumor

关 键 词：消化系统肿瘤 临床意义 

分 类 号：R735[医药卫生—肿瘤]