Clinical features of CpG island methylation in colon cancer and its prognostic significance in dMMR colon cancer
10.3760/cma.j.cn115396-20230922-00072
- VernacularTitle:CpG岛甲基化结肠癌临床特点及其在dMMR结肠癌中的预后意义
- Author:
Yuan LIU
1
;
Ruili WANG
;
Danling WANG
;
Jianning SONG
Author Information
1. 首都医科大学附属北京友谊医院检验科，北京 100050
- Keywords:
Colon;
Neoplasms;
Genes;
Mutation;
CpG island methylated phenotype;
Deficient mismatch repair
- From:
International Journal of Surgery
2024;51(1):32-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical characteristics and prognosis of CpG island methylator phenotype (CIMP+ ) colon cancer, and the significance of CIMP status in the diagnosis and prognosis prediction in defective mismatch repair (dMMR) colon cancer.Methods:The keywords "colorectal cancer" "patient" and "CpG Island Methylator Phenotype" were used to search the Gene Expression Omnibus (GEO) database, and the GSE39582 was obtained, which included the clinical data of 585 patients with colorectal cancer and the sequencing data of the whole transcriptome of the tumor tissues. After excluding 72 cases with missing CIMP values, 513 cases were included for further analysis, including 278 males and 235 females, with a mean age of (67±13) years. According to the CIMP status, they were divided into CIMP+ group ( n=93) and CIMP-group ( n=420), then compare the differences in clinical characteristics, the Kaplan-Meier survival curves were plotted to compare the overall survival and disease-free survival; 71 dMMR cases were divided into CIMP+ group ( n=43) and CIMP-group ( n=28), and the K-M curves were plotted to analyze the differences in overall survival (OS) and disease free survival (DFS). Comparisons between groups were performed by t-test, χ2 test or Mann-Whitney U nonparametric test, and the difference in survival curves was tested by Long-rank test. Results:Patients in the CIMP+ group were significantly older than those in the CIMP-group [(70.84±12.60) years vs (66.21±13.08) years, t=3.18, P=0.002]. Right colon tumors originating from the CIMP+ molecular pathway were 9.3 times more likely to be CIMP+ than those of the left colon cancers ( OR=9.3, 95% CI: 5.2-17.9). BRAF mutant colon cancer originating from CIMP+ was 215.2 times more common than BRAF wild-type colon cancer originating with CIMP+ ( OR=215.2, 95% CI: 53.2-1906.7); and patients with dMMR colon cancer originated 12.8 times more common than patients with pMMR ( OR=12.8, 95% CI: 7.0-23.9). The difference between the CIMP+ and CIMP-groups was not statistically significant in terms of overall survival and disease-free survival ( P=0.590, 0.220). In the dMMR colon cancer subgroup, CIMP status did not correlate with patients′ overall survival and disease-free survival ( P>0.05). Conclusions:CIMP+ colon cancer patients were mostly of advanced age, with tumors originating from the right colon, mostly combined with BRAF gene mutations, and manifested as mismatch repair-deficient colon cancers. CIMP status had no correlation with TNM stage and survival of colon cancers patients. There was no significant difference in the survival between dMMR colon cancers caused by CIMP+ and those caused by MMR gene mutations.
