Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu, China.
Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu, China.
Int Immunopharmacol. 2024 Jun 15;134:112162. doi: 10.1016/j.intimp.2024.112162. Epub 2024 May 3.
Epidemiological evidence has indicated the occurrence of idiopathic pulmonary fibrosis (IPF) with coexisting lung cancer is not a coincidence. The pathogenic mechanisms shared between IPF and non-small cell lung cancer (NSCLC) at the transcriptional level remain elusive and need to be further elucidated.
IPF and NSCLC datasets of expression profiles were obtained from the GEO database. Firstly, to detect the shared dysregulated genes positively correlated with both IPF and NSCLC, differentially expressed analysis and WGCNA analysis were carried out. Functional enrichment and the construction of protein-protein network were employed to reveal pathogenic mechanisms related to two diseases mediated by the shared dysregulated genes. Then, the LASSO regression was adopted for screening critical candidate biomarkers for two disorders. Moreover, ROC curves were applied to evaluate the diagnostic value of the candidate biomarkers in both IPF and NSCLC.
The 20 shared dysregulated genes positively correlated with both IPF and NSCLC were identified after intersecting differentially expressed analysis and WGCNA analysis. Functional enrichment revealed the 20 shared genes mostly enriched in extracellular region, which is critical in the organization of extracellular matrix. The protein-protein networks unrevealed the interaction of the 11 shared genes involving in collagen deposition and the connection between PYCR1 with PSAT1. PSAT1, PYCR1, COL10A1 and KIAA1683 were screened by the LASSO regression. ROC curves comprising area under the curve (AUC) verified the potential diagnostic value of PSAT1 and COL10A1 in both IPF and NSCLC.
We revealed dysregulated extracellular matrix through aberrant expression of the relevant genes, which provided further understanding for the common molecular mechanisms predisposing the occurrence of both IPF and NSCLC.
流行病学证据表明，特发性肺纤维化（IPF）合并肺癌的发生并非偶然。IPF 和非小细胞肺癌（NSCLC）在转录水平上的共同发病机制仍不清楚，需要进一步阐明。
从 GEO 数据库中获取 IPF 和 NSCLC 数据集的表达谱。首先，为了检测与 IPF 和 NSCLC 均呈正相关的共享失调基因，进行差异表达分析和 WGCNA 分析。采用功能富集和蛋白质-蛋白质网络构建，揭示由共享失调基因介导的与两种疾病相关的发病机制。然后，采用 LASSO 回归筛选两种疾病的关键候选生物标志物。此外，应用 ROC 曲线评估候选生物标志物在 IPF 和 NSCLC 中的诊断价值。
通过差异表达分析和 WGCNA 分析的交集，鉴定出与 IPF 和 NSCLC 均呈正相关的 20 个共享失调基因。功能富集揭示了 20 个共享基因主要富集在外分泌区域，这对外泌基质的组织至关重要。蛋白质-蛋白质网络揭示了 11 个共享基因涉及胶原蛋白沉积的相互作用，以及 PYCR1 与 PSAT1 之间的联系。通过 LASSO 回归筛选出 PSAT1、PYCR1、COL10A1 和 KIAA1683。ROC 曲线（包括曲线下面积（AUC））验证了 PSAT1 和 COL10A1 在 IPF 和 NSCLC 中的潜在诊断价值。
我们通过相关基因的异常表达揭示了失调的细胞外基质，为理解导致 IPF 和 NSCLC 共同发生的共同分子机制提供了进一步的认识。
