Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
Med Sci Monit. 2021 Aug 10;27:e932370. doi: 10.12659/MSM.932370.
BACKGROUND Colorectal cancer (CRC) is the second most deadly cancer in the world according to GLOBOCAN 2020 data. Accumulating evidence suggests that RNA methylation modification is also misregulated in human cancers and may be a potential ideal target for cancer treatment. MATERIAL AND METHODS m6A-related differentially expressed genes (DEGs) were identified from colon adenocarcinoma and rectum adenocarcinoma esophageal carcinoma patients with different pathological stages. The protein-protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Cox regression analysis was applied to the screening of m6A-related DEGs significantly associated with the overall survival (OS), and those selected genes were used for LASSO regression analysis to construct prognostic signature and calculate patients' risk scores. RESULTS We identified 673 m6A-related DEGs from CRC patients in different pathologic stages, and 146 of them were associated with OS. CTNNB1, TRIM37, RAB7A, CASC5/KNL1, CENPE, CCNB1, UBE2H, HSPA8, KIF1A, and FBXW4 were hub genes of the PPI network. Nine m6A-related genes were screened out to build the prognostic risk model. TNM stage, vascular invasion, and the risk score were independently related to the OS of CRC patients. CONCLUSIONS Nine candidate m6A-related mRNA biomarkers (LRRC17, NFKB1, NOS2, PCDHB2, RAB7A, RPS6KA1, RRNAD1, TLE6, and UBE2H) were found to be closely related to the clinicopathology and prognosis of colorectal cancer, indicating that they could be potential prognostic biomarkers for patients with colorectal cancer.
根据 GLOBOCAN 2020 数据，结直肠癌（CRC）是全球第二大致命癌症。越来越多的证据表明，RNA 甲基化修饰在人类癌症中也失调，可能是癌症治疗的潜在理想靶点。
从不同病理阶段的结肠腺癌、直肠腺癌和食管癌患者中鉴定出 m6A 相关差异表达基因（DEGs）。构建 DEGs 的蛋白-蛋白相互作用（PPI）网络，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。应用 Cox 回归分析筛选与总生存期（OS）显著相关的 m6A 相关 DEGs，并对这些选定基因进行 LASSO 回归分析，构建预后标志并计算患者的风险评分。
我们从不同病理阶段的 CRC 患者中鉴定出 673 个 m6A 相关 DEGs，其中 146 个与 OS 相关。CTNNB1、TRIM37、RAB7A、CASC5/KNL1、CENPE、CCNB1、UBE2H、HSPA8、KIF1A 和 FBXW4 是 PPI 网络的核心基因。筛选出 9 个 m6A 相关基因构建预后风险模型。TNM 分期、血管侵犯和风险评分与 CRC 患者的 OS 独立相关。
发现 9 个候选 m6A 相关 mRNA 生物标志物（LRRC17、NFKB1、NOS2、PCDHB2、RAB7A、RPS6KA1、RRNAD1、TLE6 和 UBE2H）与结直肠癌的临床病理和预后密切相关，表明它们可能是结直肠癌患者潜在的预后生物标志物。
