School of Public Health, Wuhan University, No. 115 of Donghu Road, Wuchang District, Wuhan, 430000, China.
Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
Sci Rep. 2021 Nov 17;11(1):22464. doi: 10.1038/s41598-021-01850-x.
Colorectal cancer (CRC), a common malignant tumor of the digestive tract, has a high incidence and mortality rate. Several recent studies have found that aging is associated with the increasing risk of cancer. Nevertheless, the expression status and function of age-related genes in CRC is still not well understood. In the study, we comprehensively analyzed the gene expression data of CRC patients from The Cancer Genome Atlas (TCGA) database. Age-related differential expression genes (age-related DEGs) in tumor tissues compared with normal tissues of CRC were further identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of age-related DEGs were performed by clusterProfiler of R. Afterwards, we used the STRING database to map the protein-protein interaction network of DEGs. We constructed prognostic model through univariate and multivariate COX regression analyses, and further evaluated their predictive power. The prognostic gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). The weighted gene co-expression network analysis (WGCNA) was used to identify key module associated with two prognostic gene signatures. Finally, we used the Metascape to perform functional enrichment analysis of genes in the key module. A total of 279 age-related DEGs were identified from the TCGA database. GO and KEGG enrichment analysis showed that the age-related DEGs were enriched in the Modulation of chemical synaptic transmission and Neuroactive ligand-receptor interaction. Moreover, we established a novel age-related gene signature (DLX2 and PCOLCE2) for overall survival in CRC, which was further predicted in both the training and validation sets. The results of GSEA demonstrated that numerous disease-related pathways were enriched in the high-risk group. We identified 43 genes related to the DLX2 and PCOLCE2 by the WGCNA co-expression network. We also found that these 43 genes were enriched in the cancer-related pathways. To sum up, the study identified an age-related gene signature for predicting the prognosis of CRC patients, which is conducive to the identification of novel prognostic molecular markers.
结直肠癌（CRC）是一种常见的消化道恶性肿瘤，其发病率和死亡率都很高。最近的几项研究发现，衰老与癌症风险的增加有关。然而，CRC 中与年龄相关的基因的表达状态和功能仍不清楚。在这项研究中，我们综合分析了来自癌症基因组图谱（TCGA）数据库的 CRC 患者的基因表达数据。进一步鉴定了肿瘤组织与 CRC 正常组织相比的与年龄相关的差异表达基因（age-related DEGs）。我们使用 R 中的 clusterProfiler 对 age-related DEGs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。之后，我们使用 STRING 数据库来映射 DEGs 的蛋白质-蛋白质相互作用网络。我们通过单变量和多变量 COX 回归分析构建了预后模型，并进一步评估了它们的预测能力。通过基因集富集分析（GSEA）探索了与预后基因特征相关的功能途径。使用加权基因共表达网络分析（WGCNA）识别与两个预后基因特征相关的关键模块。最后，我们使用 Metascape 对关键模块中的基因进行功能富集分析。我们从 TCGA 数据库中鉴定出了 279 个与年龄相关的 DEGs。GO 和 KEGG 富集分析表明，age-related DEGs 富集在化学突触传递的调节和神经活性配体-受体相互作用中。此外，我们建立了一个新的结直肠癌总生存的与年龄相关的基因特征（DLX2 和 PCOLCE2），并在训练集和验证集中进行了进一步预测。GSEA 的结果表明，许多疾病相关途径在高危组中富集。我们通过 WGCNA 共表达网络识别出与 DLX2 和 PCOLCE2 相关的 43 个基因。我们还发现这些 43 个基因富集在癌症相关途径中。总之，本研究确定了一个用于预测 CRC 患者预后的与年龄相关的基因特征，这有利于识别新的预后分子标志物。
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