结直肠癌样本免疫细胞浸润及肿瘤突变负荷分析

doi:10.3969/j.issn.1004-616x.2023.03.002

摘要/Abstract

摘要： 目的：采用生物信息学方法分析结直肠癌(CRC)样本免疫细胞浸润以及肿瘤突变负荷。方法：用CIBERSORT和ESTIMATE算法计算CRC样本中各免疫细胞的相对比例，用Spearman检验分析免疫细胞之间的相关性。基于CRC样本免疫细胞浸润比例的相似性，用ConsensusClusterPlus将样本分为免疫细胞聚类A和免疫细胞聚类B两群，Kaplan-Meier分析群间样本总生存期差异。构建CRC样本免疫细胞评分模型，依据样本免疫细胞评分，将CRC样本分为免疫细胞评分高、低两组，Kaplan-Meier分析组间样本总生存期差异，采用基因集富集分析(GSEA)研究免疫细胞评分高、低两组的基因集富集通路。整理突变数据，计算肿瘤突变负荷，依据肿瘤突变负荷将样本分为肿瘤突变负荷高、低两组。用maftool绘制突变瀑布图，用Kaplan-Meier分析肿瘤突变负荷高、低两组样本总生存期差异。结果：免疫细胞聚类A、B两群样本总生存期差异无统计学意义(P>0.05)，免疫细胞评分高组患者的总生存期较免疫细胞评分低组患者长(P=0.005)。与肠道生理功能密切相关的通路在免疫细胞评分高组样本中富集，与肿瘤形成、发展和转移密切相关的通路在免疫细胞评分低组样本中富集。肿瘤突变负荷在免疫细胞评分高、低两组间差异无统计学意义(P>0.05)，APC、TP53和KRAS基因突变频率在免疫细胞评分高、低两组样本中均较高，肿瘤突变负荷低组CRC患者总生存期长于肿瘤突变负荷高组患者(P=0.035)。结论：免疫细胞评分高组CRC患者总生存期长于免疫细胞评分低组患者，肿瘤突变负荷低组CRC患者总生存期长于肿瘤突变负荷高组患者。

关键词: 结直肠癌, 免疫细胞浸润, 肿瘤突变负荷, 生物信息学分析

Abstract: OBJECTIVE：Expression of immune cell infiltration (ICI) and tumor mutation burden (TMB) in colorectal cancer (CRC) samples were analyzed using bioinformatic analysis. METHODS：The CIBERSORT and ESTIMATE algorithms were used to calculate relative fractions of immune cells in CRC samples，and the Spearman test was used to analyze correlations among infiltrating immune cells. The ConsensusClusterPlus was used to cluster the CRC samples into ICI cluster A and ICI cluster B based on similarity of the relative fractions of immune cell infiltration. The overall survival (OS) of patients were analyzed by Kaplan-Meier. The ICI score model of CRC samples was constructed based on the signature gene A and signature gene B，and ICI scores of each CRC samples were calculated. CRC patients were divided into two groups based on the ICI scores：ICI score High and Low. The OS of patients were analyzed by Kaplan-Meier，and GSEA was used to analyze the enrichment pathways in each group. TMB was calculated and presented by maftool. Based on the TMB，the CRC patients were divided into H-TMB and L-TMB. The OS of patients between two groups were analyzed by Kaplan-Meier. RESULTS：There was no statistical difference in OS between patients in ICI clusters A and B. However，patients in the ICI score high group had longer OS than those in the ICI score low group. Gene sets which were closely related to intestinal physiological functions were enriched in the ICI score high samples，while gene sets which were closely related to tumor formation，development and metastasis were enriched in the ICI score low group. There was no significant difference in TMB between ICI score low and ICI score high samples. The frequencies of KRAS，TP53 and APC were the highest compared with that of other genes in both the ICI score low and high groups. The patients in the L-TMB group had longer OS than those in the H-TMB group. CONCLUSION：CRC patients in the ICI score high group had longer OS than those in the ICI score low group，and patienets in the L-TMB group had longer OS than those in the H-TMB group.

Key words: colorectal cancer, immune cells infiltration, tumor mutation burden, bioinformatic analysis

中图分类号:

R730.3

王娜, 王平, 何仪佳, 曾晶, 韩聪玲, 王思睿, 轩小燕. 结直肠癌样本免疫细胞浸润及肿瘤突变负荷分析[J]. 癌变·畸变·突变, 2023, 35(3): 172-177.

WANG Na, WANG Ping, HE Yijia, ZENG Jing, HAN Congling, WANG Sirui, XUAN Xiaoyan. Bioinformatic analysis of immune cell infiltration and tumor mutation burden in colorectal cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(3): 172-177.

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