Department of Respiratory and Critical Care Medicine, West China School of Medicine and West China Hospital, Sichuan University, Chengdu 610041, China.
Comb Chem High Throughput Screen. 2022;25(9):1498-1506. doi: 10.2174/1386207324666210707105634.
Currently, there are no reliable diagnostic and prognostic markers for Malignant Pleural Mesothelioma (MPM). The objective of this study was to identify hub genes that could be helpful for diagnosis and prognosis in MPM by using bioinformatics analysis.
The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Weighted Gene Co-expression Network Analysis (WGCNA), LASSO regression analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) were performed to identify hub genes and their functions.
A total of 430 upregulated and 867 downregulated genes in MPM were identified based on the GSE51024 dataset. According to the WGCNA analysis, differentially expressed genes were classified into 8 modules. Among them, the pink module was most closely associated with MPM. According to genes with GS > 0.8 and MM > 0.8, six genes were selected as candidate hub genes (NUSAP1, TOP2A, PLOD2, BUB1B, UHRF1, KIAA0101) in the pink module. In the LASSO model, three genes (NUSAP1, PLOD2, and KIAA0101) were identified with non-zero regression coefficients and were considered as hub genes among the 6 candidates. The hub gene-based LASSO model can accurately distinguish MPM from controls (AUC=0.98). Moreover, the high expression level of KIAA0101, PLOD2, and NUSAP1 was associated with poor prognosis compared to the low level in Kaplan-Meier survival analyses. After further multivariate Cox analysis, only KIAA0101 (HR = 1.55, 95% CI = 1.05-2.29) was identified as an independent prognostic factor among these hub genes. Finally, GSEA revealed that high expression of KIAA0101 was closely associated with 10 signaling pathways.
Our study identified several hub genes relevant to MPM, including NUSAP1, PLOD2, and KIAA0101. Among these genes, KIAA0101 appears to be a useful diagnostic and prognostic biomarker for MPM, which may provide new clues for MPM diagnosis and therapy.
目前，恶性胸膜间皮瘤（MPM）尚无可靠的诊断和预后标志物。本研究旨在通过生物信息学分析，鉴定有助于 MPM 诊断和预后的关键基因。
从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）中下载基因表达谱。采用加权基因共表达网络分析（WGCNA）、LASSO 回归分析、Cox 回归分析和基因集富集分析（GSEA），鉴定关键基因及其功能。
根据 GSE51024 数据集，共鉴定出 430 个上调和 867 个下调的 MPM 基因。根据 WGCNA 分析，差异表达基因被分为 8 个模块。其中，粉色模块与 MPM 最密切相关。根据 GS＞0.8 和 MM＞0.8，在粉色模块中选择 6 个候选关键基因（NUSAP1、TOP2A、PLOD2、BUB1B、UHRF1、KIAA0101）。在 LASSO 模型中，三个基因（NUSAP1、PLOD2 和 KIAA0101）具有非零回归系数，被认为是 6 个候选基因中的关键基因。基于关键基因的 LASSO 模型可准确区分 MPM 与对照（AUC=0.98）。此外，在 Kaplan-Meier 生存分析中，与低表达水平相比，高表达水平的 KIAA0101、PLOD2 和 NUSAP1 与预后不良相关。进一步进行多变量 Cox 分析后，仅 KIAA0101（HR=1.55，95%CI=1.05-2.29）被鉴定为这些关键基因中的独立预后因素。最后，GSEA 显示 KIAA0101 的高表达与 10 个信号通路密切相关。
本研究鉴定了与 MPM 相关的几个关键基因，包括 NUSAP1、PLOD2 和 KIAA0101。其中，KIAA0101 似乎是 MPM 有用的诊断和预后生物标志物，可为 MPM 的诊断和治疗提供新的线索。
