摘要
目的 分析肿瘤突变负荷(TMB)及基因差异表达与卵巢癌患者预后的关系,并依据TMB背景下获取免疫细胞浸润分布情况分析其对卵巢癌患者预后的影响。方法 从癌症基因组图谱(TCGA)数据库获取卵巢癌患者体细胞突变数据、基因转录组数据及临床信息,利用R软件对数据进行生存分析及差异分析,采用非负矩阵分解CIBERSORT算法确定免疫细胞与TMB亚型之间的相关性。结果 纳入卵巢癌体细胞突变数据下载的样本,其中突变种类最多的为错义突变;变异类型中单核苷酸多态性(SNP)占比最大。单核苷酸变异种类(SNV)中的C>T转换最多,C>A次之;突变频率最高的基因为TP53,其次为TTN,但二者是否突变与生存时间无关(P=0.921、0.431);BRAC1是否突变与生存时间无关(P=0.110);TMB水平与卵巢癌总生存时间无关(P=0.053),与无进展生存时间相关(P=0.007)。高TMB组与低TMB组之间筛选出5个差异表达基因,分别是AGR3、IGSF23、ALDH1A2、GNAO1、FCRL6;其中IGSF23为上调基因(在差异分析中发现,在高TMB水平下,IGSF23呈现高表达),其余4个为下调基因。对已筛选出的差异表达基因进行生存分析:ALDH1A2与总生存时间相关(P=0.048);AGR3及IGSF23与无进展生存相关(P=0.037、0.024)。对两组之间浸润性免疫细胞的占比进行差异分析,发现活跃B细胞及活跃自然杀伤细胞在低TMB组中占比更高(P<0.05),M0、M1巨噬细胞的浸润程度在高TMB组中占比较高,M2巨噬细胞在低TMB组中占比较高。结论 TMB与卵巢癌的预后存在相关性,高TMB能够获得更长的生存时间;IGSF23的表达水平可能更好地作为卵巢癌患者预后判断的指标。M1巨噬细胞在卵巢癌中的抗肿瘤作用得到了验证。
Objective Analysis of the relationship between tumor mutation burden(TMB)and gene differential expression and prognosis of ovarian cancer patients.According to the distribution of immune cell infiltration in the background of TMB,its influence on the prognosis of ovarian cancer patients was analyzed.Methods The somatic mutation data,gene transcriptome data and clinical information of ovarian cancer patients were obtained from the cancer genome atlas(TCGA)database,and R software was used to conduct survival analysis and differential analysis of the data.Correlations between immune cells and TMB subtypes was determined by non-negative matrix decomposition CIBERSORT algorithm.Results Among the samples included in the download of ovarian cancer somatic mutation data,the most common type of mutation is missense mutation.Single nucleotide polymorphism(SNP)accounts for the largest proportion of variation types.The single nucleotide variant(SNV)has the highest C>T conversion,followed by C>A.The gene with the highest mutation frequency is TP53,followed by TTN,there was no correlation between mutation and survival time(P=0.921,0.431).There was no correlation between BRAC1 mutation and survival time(P=0.110).TMB level was not associated with overall survival time of ovarian cancer(P=0.053),but it was associated with progression-free survival time(P=0.007).Five differentially expressed genes were screened between the high TMB group and the low TMB group,namely AGR3,IGSF23,ALDH1A2,GNAO1,and FCRL6.Among them,IGSF23 was an up-regulated gene(in the differential analysis,it was found thatIGSF23 was highly expressed under high TMB levels),and the remaining 4 genes were down-regulated.Survival analysis was performed on the screened differentially expressed genes:ALDH1A2 was associated with overall survival time(P=0.048);AGR3 and IGSF23 were associated with progression-free survival(P=0.037,0.024).Analysis of the difference in the proportion of infiltrating immune cells between the two groups showed that the proportion of active B cells and active NK cells was higher in the low TMB group(P<0.05),and the infiltration degree of M0 and M1 macrophages accounted for a higher proportion in the high TMB group,and M2 macrophages accounted for a higher proportion in the low TMB group.Conclusions There is a correlation between TMB and the prognosis of ovarian cancer,and high TMB is associated with longer survival time;the expression level of IGSF23 may be a better indicator for the prognosis of ovarian cancer patients.The antitumor effect of M1 macrophages in ovarian cancer has been verified.
作者
柏诗玉
方彩云
龚坤雪
黄银银
赵锐
王云
李肖肖
BAI Shigu;FANG Caiyun;GONG Kunxue;HUANG Yinyin;ZHAO Rui;WANG Yiun;LI Xiaoxiao(Department of Gmecology,Afliated Hospital of Hubei Uniersity of Medicine,Shiyan 44000,Hubei,China;Department of Gynecology,Taihe Hospital,Shiyan 442000,Hubei,China)
出处
《中国性科学》
2023年第8期76-82,共7页
Chinese Journal of Human Sexuality
基金
十堰市太和医院院级课题基金项目(2020JJXM053)。
关键词
卵巢癌
肿瘤突变负荷
预后
生存分析
Ovarian cancer
Tumor mutation burden
Prognosis
Survival analysis