作者：孙中尚，高志颖，潘峰，王宏刚，潘振国

单位：南京医科大学附属淮安第一医院 消化内科， 江苏 淮安223300

Authors: Sun Zhongshang，Gao Zhiying，Pan Feng，Wang Honggang，Pan Zhenguo

Unit: Department of Gastroenterology，the Affliated Huai'an First People's Hospital of Nanjing Medical University，Huai'an 223300，Jiangsu，China

摘要：

目的 应用生物信息学方法探究结直肠腺瘤-腺癌序列中的关键基因，筛选出可用于评估腺瘤恶变风险的标志物。方法 搜索GEO数据库中结直肠腺瘤与腺癌相关数据集，筛选出关键差异基因，并对关键差异基因行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）信号通路富集分析，通过构建蛋白质互作网络（PPI）筛选出主效基因，利用GEPIA数据库绘制生存曲线分析主效基因与结直肠腺癌预后的关系。结果 在GSE50115和GSE46157两个数据集中，筛选出42个关键差异基因。GO功能分析表面，关键差异基因主要富集在组织细胞外基质、胶原构成的细胞外基质和细胞外基质结构组成等功能，KEGG信号通路分析显示主要富集于细胞外基质受体相互作用。PPI共筛选出6个主效基因，其中α1-Ⅰ型胶原基因（COL1A1）和α1-Ⅻ型胶原基因（COL12A1）表达量与结直肠腺癌患者预后呈负相关。结论 COL1A1和COL12A1在结直肠腺瘤-腺癌序列中发挥重要作用，可作为判断腺瘤恶变风险的标志物。

关键词：结直肠腺瘤-腺癌序列； 结直肠腺瘤恶变风险； 生物信息分析

Abstract：

Objective To apply a bioinformatics approach to explore key genes in colorectal adenoma-adenocarcinoma sequences and screen for markers that can be used to assess the risk of adenoma malignancy. Method We searched the GEO database for colorectal adenoma -adenocarcinoma related datasets, screened out key differential genes，performed gene ontology （GO） function and Kyoto Encyclopedia of Genomes（KEGG） signaling pathway enrichment analysis of key differential genes，identified master-effect genes by constructing protein interaction network （PPI） network，and analyzed master-effect genes by plotting survival curves using GEPIA database The relationship with prognosis of colorectal adenocarcinoma was analyzed by drawing survival curves using GEPIA database. Result The results showed that 42 key differential genes were screened in the GSE50115 and GSE46157 datasets，and the GO functional analysis showed that the key differential genes were mainly enriched in the functions of tissue extracellular matrix ，extracellular matrix composed of collagen and extracellular matrix structural composition，and the KEGG signaling pathway analysis showed that they were mainly enriched in extracellular matrix receptor interactions. A total of 6 key genes were screened by PPI，among which the expression of Collagen alpha-1 （Ⅰ） chain （COL1A1） and collagen type Ⅻ alpha 1 chain （COL12A1） was negatively correlated with the prognosis of colorectal adenocarcinoma patients. Conclusion COL1A1 and COL12A1 play an important role in the colorectal adenoma-adenocarcinoma sequence and can be used as markers to determine the risk of adenoma malignancy.

Key Words: Colorectal adenoma-adenocarcinoma sequence; Colorectal adenoma malignancy risk; Bioinformatic analysis