Liu Chuan, Wang Ting, Yang Jiahui, Zhang Jixiang, Wei Shuchun, Guo Yingyun, Yu Rong, Tan Zongbiao, Wang Shuo, Dong Weiguo
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Geriatric, West China Hospital of Sichuan University, Chengdu, China.
Front Oncol. 2022 Apr 22;12:878805. doi: 10.3389/fonc.2022.878805. eCollection 2022.
This study aimed to investigate the distant metastasis pattern from newly diagnosed colorectal cancer (CRC) and also construct and validate a prognostic nomogram to predict both overall survival (OS) and cancer-specific survival (CSS) of CRC patients with distant metastases.
Primary CRC patients who were initially diagnosed from 2010 to 2016 in the SEER database were included in the analysis. The independent risk factors affecting the OS, CSS, all-cause mortality, and CRC-specific mortality of the patients were screened by the Cox regression and Fine-Gray competitive risk model. The nomogram models were constructed to predict the OS and CSS of the patients. The reliability and accuracy of the prediction model were evaluated by consistency index (C-index) and calibration curve. The gene chip GSE41258 was downloaded from the GEO database, and differentially expressed genes (DEGs) were screened by the GEO2R online tool ( < 0.05, |logFC|>1.5). The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway and Gene Ontology (GO) annotation and String website were used for enrichment analysis and protein-protein interaction (PPI) analysis of DEGs, respectively, and Cytoscape software was used to construct PPI network and screen function modules and hub genes.
A total of 57,835 CRC patients, including 47,823 without distant metastases and 10,012 (17.31%) with metastases, were identified. Older age, unmarried status, poorly differentiated or undifferentiated grade, right colon site, larger tumor size, N2 stage, more metastatic sites, and elevated carcinoembryonic antigen (CEA) might lead to poorer prognosis (all < 0.01). The independent risk factors of OS and CSS were included to construct a prognosis prediction model for predicting OS and CSS in CRC patients with distant metastasis. C-index and calibration curve of the training group and validation group showed that the models had acceptable predictive performance and high calibration degree. Furthermore, by comparing CRC tissues with and without liver metastasis, 158 DEGs and top 10 hub genes were screened. Hub genes were mainly concentrated in liver function and coagulation function.
The big data in the public database were counted and transformed into a prognostic evaluation tool that could be applied to the clinic, which has certain clinical significance for the formulation of the treatment plan and prognostic evaluation of CRC patients with distant metastasis.
本研究旨在调查新诊断结直肠癌(CRC)的远处转移模式,并构建和验证一个预后列线图,以预测发生远处转移的CRC患者的总生存期(OS)和癌症特异性生存期(CSS)。
纳入2010年至2016年在SEER数据库中初诊的原发性CRC患者进行分析。通过Cox回归和Fine-Gray竞争风险模型筛选影响患者OS、CSS、全因死亡率和CRC特异性死亡率的独立危险因素。构建列线图模型以预测患者的OS和CSS。通过一致性指数(C-index)和校准曲线评估预测模型的可靠性和准确性。从GEO数据库下载基因芯片GSE41258,使用GEO2R在线工具筛选差异表达基因(DEG)(<0.05,|logFC|>1.5)。分别使用京都基因与基因组百科全书(KEGG)通路、基因本体(GO)注释和String网站对DEG进行富集分析和蛋白质-蛋白质相互作用(PPI)分析,并使用Cytoscape软件构建PPI网络并筛选功能模块和枢纽基因。
共纳入57,835例CRC患者,其中47,823例无远处转移,10,012例(17.31%)有远处转移。年龄较大、未婚状态、低分化或未分化分级、右半结肠部位、肿瘤较大、N2期、转移部位较多以及癌胚抗原(CEA)升高可能导致预后较差(均<0.01)。纳入OS和CSS的独立危险因素,构建用于预测发生远处转移的CRC患者OS和CSS的预后预测模型。训练组和验证组的C-index和校准曲线表明模型具有可接受的预测性能和较高的校准度。此外,通过比较有和无肝转移的CRC组织,筛选出158个DEG和前10个枢纽基因。枢纽基因主要集中在肝功能和凝血功能方面。
对公共数据库中的大数据进行统计并转化为可应用于临床的预后评估工具,这对制定发生远处转移的CRC患者的治疗方案和预后评估具有一定的临床意义。