Xu Xiaoming, Wang Jingzhi
Department of Gastroenterology, Jining First People's Hospital, Jining, China.
Department of Radiotherapy Oncology, The Affiliated Yancheng First Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China.
Front Genet. 2023 Mar 6;14:1088091. doi: 10.3389/fgene.2023.1088091. eCollection 2023.
Colon adenocarcinoma (COAD) is one of the most frequent malignant lesions of the digestive system in humans, with an insidious onset. At the time of diagnosis, most of them have developed to the middle and late stages, and cancer cells have metastasized, and the prognosis is poor. Treatment options for progressive COAD are limited, and despite the promise of immunotherapy, immunotherapy response rates are low. The assembly and disaggregation of focal adhesion are critical for the directional migration of tumor cells to different sites, and it is unclear whether focal adhesion-related genes are involved in the development and prognosis of colon adenocarcinoma. This study aimed to investigate the role of focal adhesion genes in the occurrence and prognosis of COAD. We obtained datasets of COAD patients, including RNA-sequencing data and clinical information, from the TCGA and GEO databases (GSE17538 and GSE39582). Through CNMF clustering, two molecular subtypes with different expression patterns of focal adhesion genes were identified, and it was found that the molecular subtype with low expression of focal adhesion genes had better prognosis. Then the prediction signature was constructed by LASSO-Cox regression model, and the receiver operating characteristic (ROC) curve showed that the 4-gene signature had a good prediction effect on COAD 1-, 2-, and 3-year OS. Gene function enrichment analysis showed that the high-risk group was mainly enriched in immune and adhesion-related signaling pathways, suggesting that focal adhesion genes may affect the development and prognosis of COAD by regulating the immune microenvironment and tumor metastasis. The interaction between focal adhesion genes and immunity during the occurrence of COAD may help improve the response rate of immunotherapy, which also provides new ideas for the molecular mechanism and targeted therapy in COAD.
结肠腺癌(COAD)是人类消化系统最常见的恶性病变之一,起病隐匿。在诊断时,大多数患者已发展至中晚期,癌细胞已发生转移,预后较差。进展期COAD的治疗选择有限,尽管免疫疗法前景广阔,但免疫疗法的反应率较低。粘着斑的组装和解聚对于肿瘤细胞向不同部位的定向迁移至关重要,目前尚不清楚粘着斑相关基因是否参与结肠腺癌的发生和预后。本研究旨在探讨粘着斑基因在COAD发生和预后中的作用。我们从TCGA和GEO数据库(GSE17538和GSE39582)中获取了COAD患者的数据集,包括RNA测序数据和临床信息。通过CNMF聚类,鉴定出粘着斑基因表达模式不同的两种分子亚型,发现粘着斑基因低表达的分子亚型预后较好。然后通过LASSO-Cox回归模型构建预测特征,受试者工作特征(ROC)曲线显示,4基因特征对COAD的1年、2年和3年总生存期具有良好的预测效果。基因功能富集分析表明,高危组主要富集于免疫和粘附相关信号通路,提示粘着斑基因可能通过调节免疫微环境和肿瘤转移影响COAD的发生和预后。COAD发生过程中粘着斑基因与免疫之间的相互作用可能有助于提高免疫疗法的反应率,这也为COAD的分子机制和靶向治疗提供了新的思路。