老年结肠癌患者肿瘤异质性分析:一项基于SEER数据库和TCGA数据库的研究

Bioinformatics analysis of tumor heterogeneity of aging patients with colonic cancer:a study based on SEER database and TCGA database

目的基于美国国立癌症研究院监测、流行病学和结果(SEER)数据库和癌症基因组图谱(TCGA)数据库探索老年结直肠患者临床预后特点及肿瘤异质性。方法从SEER数据库中提取2010至2015年期间结肠癌患者相关临床病理信息,根据患者年龄,将患者分为6个组(<45岁,45~54岁,55~64岁,65~74岁,75~84岁,≥85岁),依据结肠癌预后探索老年人与非老年人的年龄分切点。从TCGA数据库下载结肠癌患者的转录组测序结果、体细胞突变结果及临床数据,分析老年组与非老年组肿瘤突变负荷、免疫微环境等指标的差异,并通过对潜在的靶基因进行功能富集及信号通路分析。结果Kaplan-Meier曲线结果显示<45岁、45~54岁、55~64岁3个年龄组结肠癌患者总体生存率(OS)、肿瘤特异性生存率(CSS)明显优于75~84岁及≥85岁年龄组患者。COX单因素分析显示,发现65~74岁、75~84岁及≥85岁年龄组结肠癌患者OS显著差于<45岁年龄组,75~84岁及≥85岁年龄组结肠癌患者CSS,显著差于<45岁年龄组。以此确定老年组与非老年组的年龄分切点定为75岁。以75岁为界,老年组OS、CSS均差于非老年组,老年组总死亡风险和肿瘤特异性死亡风险分别是非老年组的1.904倍和1.393倍。免疫微环境分析中,两组间有7种免疫细胞相对丰度存在不同,其中自然杀伤T细胞差异最显著,老年组患者肿瘤突变负荷和肿瘤免疫评分显著高于非老年组,但两组间基质评分未见统计学差异。老年组患者免疫检查点分子包括PD1、PD-L1、PD-L2、CTLA-4和CD80表达上调。结论基于SEER和TCGA数据库,发现老年结肠癌患者预后明显差于非老年患者,且两组在肿瘤突变负荷、肿瘤微环境存在显著差异。

Objective To explore the clinical prognostic characteristics and tumor heterogeneity in elderly patients with colonic cancer based on The Surveillance,Epidemiology,and End Results(SEER)and The Cancer Genome Atlas(TCGA)databases.Methods The clinicopathological information of patients with colonic cancer confirmed by pathology from 2010 tO_(2)015 was extracted from the SEER database.According to the age of the patients,the patients were divided into six groups(<45 years old,45-54 years old,55-64 years old,65-74 years old,75-84 years old,≥85 years old).The age cut-off points of the elderly and non-elderly patients were explored according to the prognosis of colonic cancer.The transcriptome sequencing results,somatic mutation results,and clinical data of colonic cancer patients were downloaded from the TCGA database.The differences in tumor mutation burden,and immune microenvironment between the elderly and non-elderly groups were analyzed,and functional enrichment and signaling pathway analysis of potential target genes were performed.Results The Kaplan-Meier curve showed that the overall survival(OS)and cancer-specific survival(CSS)of patients aged<45 years,45-54 years,and 55-64 years were significantly better than those of patients aged 75-84 years and≥85 years.COX univariate analysis showed that the OS of colonic cancer patients aged 65-74 years,75-84 years,and≥85 years was significantly worse than that of patients aged<45 years,and the CSS of colonic cancer patients aged 75-84 years and≥85 years was significantly worse than that of patients aged<45 years.The cut-off point of age for the elderly group and the non-elderly group was 75 years.The OS and CSS of the elderly group were worse than those of the non-elderly group.The risk of total death and cancer-specific death in the elderly group was 1.904 and 1.393 times higher than in the non-elderly group,respectively.In the immune microenvironment analysis,there were differences in the relative abundance of 7 immune cells between the two groups,among which natural killer T cells had the most significant difference.The tumor mutation burden and tumor immune score in the elderly group were significantly higher than in the non-elderly group.However,the two groups had no significant difference in matrix scores.The expression of immune checkpoint molecules,including PD1,PD-L1,PD-L2,CTLA-4,and CD80,was up-regulated in the elderly group.Conclusion Based on SEER and TCGA databases,the prognosis of elderly colonic cancer patients was significantly worse than that of non-elderly patients,and there were significant differences in tumor mutation burden and tumor microenvironment between the two groups.