基于多组学分析CIP2A在肝内胆管癌中的作用与预后相关性的生物信息学分析  

Bioinformatics based upon multiomic analysis of the role of CIP2A in cholangiocarcinoma and its prognostic correlation

作　　者：哈力木拉提·吾布力卡斯木 吐尔地·阿不来提 赖天伟 刘郁[1] 于鹏[1] 吾买尔江·买买提[1] Wubulikasimu Halimulati;Abulaiti Tuerdi;Lai Tianwei;Liu Yu;Yu Peng;Maimaiti Wumaierjiang(Institute of Traditional Chinese Medicine&Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Department I of General Surgery,Fourth Affiliated Hospital,Xinjiang Medical University,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区中医药研究院、新疆维吾尔自治区中医医院、新疆医科大学第四附属医院普外一科,新疆乌鲁木齐830000

出　　处：《腹部外科》2024年第6期418-424,共7页Journal of Abdominal Surgery

基　　金：新疆维吾尔自治区自然科学基金面上项目(2020D01C136)。

摘　　要：目的分析CIP2A在肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)中的表达及其在肿瘤特征相关性分析。方法选取2010年1月至2020年12月在新疆医科大学第四附属医院手术治疗的ICC病人66例,收集病人一般资料及临床病理参数,收集病人病理组织标本。采用肿瘤数据库GEPIA2分析CIP2A在ICC中的表达;在肿瘤病人样本中通过免疫印迹、实时荧光定量PCR(qRT-PCR)以及免疫组织化学染色法检测CIP2A的表达水平,通过免疫组织化学染色法分析CIP2A表达水平与病人临床病理参数关系。GEPIA2分析ICC中CIP2A表达与癌症总生存期、无病生存期的关系;体外培养胆管癌RBE细胞系,通过siRNA转染沉默CIP2A后进行转录组测序,初步分析与CIP2A相关基因和信号通路。结果与癌旁组织相比,胆管癌组织中CIP2A mRNA和蛋白水平显著升高。CIP2A高表达与肿瘤分化程度、脉管侵犯和淋巴结转移有关(P<0.05)。此外,CIP2A与肿瘤微环境、蛋白多糖调控、PI3K-AKT信号通路、脂代谢、核糖体调控等通路有关。结论CIP2A的高表达与ICC临床特征存在相关性,通过多组学结合临床特征分析,有助于从临床肿瘤样本角度阐述CIP2A在ICC发生发展中的作用。该研究为ICC进展的分子机制提供理论依据以及潜在的治疗靶点。Objective To explore the expression of CIP2A in intrahepatic cholangiocarcinoma(ICC)and examine its correlation with tumor characteristics.Methods Between 2010 and 2020,ICC and adjacent normal tissues were harvested from 66 operated ICC patients.General profiles,clinical pathological parameters and tissue samples were collected.The expression of CIP2A in ICC was analyzed by the database of GEPIA2.Western blot,real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)and immunohistochemical stain were utilized for detecting the expression level of CIP2A.The relationship between CIP2A expression level and clinical pathological parameters was analyzed by immunohistochemical stain.The database of GEPIA2 was accessing for examining the relationship between CIP2A expression and overall survival and disease-free survival.RBE cell line was cultured in vitro.After silencing CIP2A by siRNA transfection,transcriptome sequencing was performed to preliminarily analyze the genes and signal pathways related to CIP2A.Results As compared with adjacent tissues,the levels of CIP2A mRNA and protein spiked markedly in ICC.A high expression of CIP2A was associated with tumor differentiation,vascular invasion and lymph node metastasis(P<0.05).Furthermore,CIP2A was correlated closely with tumor microenvironment,proteoglycan regulation,PI3K-AKT signaling pathway,lipid metabolism and ribosome regulation pathways.Conclusion A high expression of CIP2A is correlated closely with the clinical characteristics of ICC.Combining omics with clinical feature analysis may help to elucidate the role of CIP2A in the occurrence and development of ICC from the perspective of clinical tumor samples.This study provides theoretical rationales and potential therapeutic targets for the molecular mechanism of ICC progression.

关 键 词：CIP2A 蛋白磷酸酚2A 肝内胆管癌 转录组测序 生物信息学 

分 类 号：R735.8[医药卫生—肿瘤]