Shi Hanyu, Sun Liang, Liu Bin
Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People's Armed Police Force, Dingzhou, Hebei, 073099, China.
Department of Pulmonary and Critical Care, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, 300162, China.
J Cancer. 2023 Jun 4;14(9):1635-1647. doi: 10.7150/jca.83407. eCollection 2023.
The basement membrane (BM), as a critical component of the extracellular matrix, plays a role in cancer progression. However, the role of the BM in lung adenocarcinoma (LUAD) remains unclear. A total of 1383 patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled in the study, and BM-related differentially expressed genes (BM-DEGs) were screened using weighted gene coexpression network analysis (WGCNA) and differential expression analysis. We next built a prognostic model using Cox regression analysis and separated patients into two groups based on the median risk score. This signature was validated with in vitro experiments, and its mechanism was investigated by enrichment and tumour microenvironment analyses. We also evaluated whether this signature could predict sensitivity to chemotherapy and immunotherapy. Finally, single-cell RNA sequencing analysis was utilized to analyse the expression of signature genes in different cells. Thirsty-seven BM-DEGs were discovered, and a prognostic signature based on 4 BM-DEGs (, , and ) was obtained in the TCGA cohort and validated in GEO cohorts. Survival curves and ROC curve analysis demonstrated that the risk score was a significant predictor of survival in all cohorts even when considering the effect of other clinical indexes. Low-risk patients had longer survival times, higher immune cell infiltration levels and better immunotherapeutic responses. Single-cell analysis showed that and were overexpressed in fibroblasts and cancer cells, respectively, compared to normal cells. This study evaluated the clinical role of the BM in LUAD and primarily explored its mechanism.
基底膜（BM）作为细胞外基质的关键组成部分，在癌症进展中发挥作用。然而，BM在肺腺癌（LUAD）中的作用仍不清楚。本研究纳入了来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）队列的1383例患者，并使用加权基因共表达网络分析（WGCNA）和差异表达分析筛选出与BM相关的差异表达基因（BM-DEGs）。接下来，我们使用Cox回归分析建立了一个预后模型，并根据中位风险评分将患者分为两组。该特征通过体外实验进行了验证，并通过富集分析和肿瘤微环境分析对其机制进行了研究。我们还评估了该特征是否可以预测化疗和免疫治疗的敏感性。最后，利用单细胞RNA测序分析来分析特征基因在不同细胞中的表达。我们发现了37个BM-DEGs，并在TCGA队列中获得了基于4个BM-DEGs（、、和）的预后特征，并在GEO队列中进行了验证。生存曲线和ROC曲线分析表明，即使考虑其他临床指标的影响，风险评分仍是所有队列中生存的重要预测指标。低风险患者的生存时间更长，免疫细胞浸润水平更高，免疫治疗反应更好。单细胞分析表明，与正常细胞相比，和成分别在成纤维细胞和癌细胞中过表达。本研究评估了BM在LUAD中的临床作用，并初步探讨了其机制。
