Liu Kai, Wang Jie-Fu, Zhan Yang, Kong Da-Lu, Wang Cui
Department of Colorectal Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
J Gastrointest Oncol. 2021 Feb;12(1):79-88. doi: 10.21037/jgo-21-28.
Colorectal cancer (CRC) is one of the most common cancers. The aim of our study was to explore its related mutations, identify novel mutation markers, and construct predictive models for postoperative CRC patients, so as to provide evidence for the diagnosis, treatment, and prognosis of CRC.
A total 50 CRC patients were collected, and the mutations in tissue samples were detected through next-generation sequencing (NGS). Meanwhile, 246 CRC cases with complete mutation data were downloaded from The Cancer Genome Atlas (TCGA) database. Afterwards, the co-mutations in both clinical and TCGA cohorts were identified, and the high-frequency mutation genes were selected. Subsequently, functional enrichment analysis was performed, and overall survival (OS) and progression-free survival (PFS) predictive models were constructed.
In all, 18 out of 238 co-mutation genes mutated in at least 20% of the samples and were selected out as common high-frequency mutation genes. They were significantly enriched in 460 Gene Ontology (GO) terms and 87 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (P<0.05), which were closely related to the occurrence and development of CRC. Among the 18 genes, , histone lysine methyltransferase 2C (), and cAMP-response element binding protein-BP () were respectively associated with tumor position, stage, and PFS (P<0.05), and could be considered as potential biomarkers of CRC. Finally, OS and PFS predictive models were constructed and verified using the 50 clinical cases, with both models demonstrating high fitting degrees useful for predicting the OS and PFS of CRC patients.
, , and were found to be prospective biomarkers for the diagnosis and prognosis of CRC. The prognosis prediction models had high sensitivity and could be used to predict the OS and PFS of CRC patients.
结直肠癌（CRC）是最常见的癌症之一。本研究的目的是探索其相关突变，识别新的突变标志物，并为CRC术后患者构建预测模型，从而为CRC的诊断、治疗和预后提供依据。
共收集50例CRC患者，通过二代测序（NGS）检测组织样本中的突变。同时，从癌症基因组图谱（TCGA）数据库下载246例具有完整突变数据的CRC病例。之后，确定临床队列和TCGA队列中的共突变，选择高频突变基因。随后进行功能富集分析，并构建总生存期（OS）和无进展生存期（PFS）预测模型。
在238个共突变基因中，共有18个在至少20%的样本中发生突变，并被选为常见的高频突变基因。它们在460个基因本体论（GO）术语和87条京都基因与基因组百科全书（KEGG）通路中显著富集（P<0.05），这些通路与CRC的发生和发展密切相关。在这18个基因中，组蛋白赖氨酸甲基转移酶2C（）和环磷酸腺苷反应元件结合蛋白BP（）分别与肿瘤位置、分期和PFS相关（P<0.05），可被视为CRC的潜在生物标志物。最后，使用50例临床病例构建并验证了OS和PFS预测模型，两个模型均显示出高拟合度，可用于预测CRC患者的OS和PFS。
发现、和是CRC诊断和预后的前瞻性生物标志物。预后预测模型具有高敏感性，可用于预测CRC患者的OS和PFS。
