Identification of Genes and Construction of Prognostic Model of Lung Adenocarcinoma Based on Propionate Metabolism-Related Genes.

IF 2.3 Q3 ONCOLOGY

World Journal of Oncology Pub Date : 2026-01-04 eCollection Date: 2026-04-01 DOI:10.14740/wjon2680

Min Min Li, Wei Jia Fu, Ying Zhou, Huan Huan Zhang, Hai Ning Li, Chu Zhang, Jin Yang

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引用次数: 0

Abstract

Background: Dysregulation of propionate metabolism can enhance the invasive properties of lung adenocarcinoma (LUAD) cells and increase their metastatic potential. Therefore, we constructed a predictive model based on propionate metabolism-related genes (PMRGs) to evaluate the prognosis of patients with LUAD.

Methods: mRNA expression profiles and clinical data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The predictive model was constructed using least absolute shrinkage and selection operator (LASSO). The associations between the risk score and tumor prognosis, immune infiltration, drug sensitivity, signaling pathways, and clinical features were evaluated using the CIBERSORT algorithm, the Genomics of Drug Sensitivity in Cancer (GDSC) database, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and nomogram analyses. For hub genes, motif enrichment, genome-wide association study (GWAS) analysis and single-cell analysis were performed. Expression differences between LUAD cells and normal lung epithelial cells were validated using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: We established a LUAD prognostic model containing 16 hub genes. The area under the receiver operating characteristic curve (AUC) values for the model were 0.722 (1-year overall survival (OS)), 0.696 (3-year OS), and 0.700 (5-year OS). GSVA revealed significant enrichment in the G2/M checkpoint, E2F targets, and glycolysis pathways. GSEA indicated enrichment of the hypoxia-inducible factor-1 (HIF-1), interleukin (IL)-17, and p53 signaling pathways. Transcription factor analysis identified the motif cisbp-M4287 as the most significantly enriched, with a normalized enrichment score (NES) of 5.9. qRT-PCR results showed that the expression of ADIPOQ, CYP27A1, and GCDH was downregulated, while the expression of SERPINE1 was upregulated. No statistically significant differences were observed in the expression of CYP17A1 and EHHADH.

Conclusions: A novel prognostic model based on PMRGs was established to predict overall survival in LUAD patients.

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基于丙酸代谢相关基因的肺腺癌基因鉴定及预后模型构建。

背景：丙酸代谢失调可增强肺腺癌（LUAD）细胞的侵袭性，增加其转移潜能。因此，我们构建了基于丙酸代谢相关基因（PMRGs）的预测模型来评估LUAD患者的预后。方法：通过Cancer Genome Atlas （TCGA）和Gene expression Omnibus （GEO）获取LUAD患者mRNA表达谱和临床资料。采用最小绝对收缩和选择算子（LASSO）建立预测模型。使用CIBERSORT算法、肿瘤药物敏感性基因组学（GDSC）数据库、基因集变异分析（GSVA）、基因集富集分析（GSEA）和nomogram分析来评估风险评分与肿瘤预后、免疫浸润、药物敏感性、信号通路和临床特征之间的关系。对于枢纽基因，进行了基序富集、全基因组关联研究（GWAS）和单细胞分析。采用定量实时聚合酶链反应（qRT-PCR）验证LUAD细胞与正常肺上皮细胞的表达差异。结果：建立了包含16个枢纽基因的LUAD预后模型。该模型的受试者工作特征曲线下面积（AUC）值分别为0.722（1年总生存期）、0.696（3年生存期）和0.700（5年生存期）。GSVA在G2/M检查点、E2F靶点和糖酵解途径中显著富集。GSEA显示缺氧诱导因子-1 （HIF-1）、白细胞介素(IL)-17和p53信号通路富集。转录因子分析发现，基序cisbp-M4287富集程度最高，其标准化富集评分（NES）为5.9。qRT-PCR结果显示，ADIPOQ、CYP27A1、GCDH表达下调，SERPINE1表达上调。CYP17A1和EHHADH的表达差异无统计学意义。结论：建立了一种基于PMRGs的新型预后模型来预测LUAD患者的总生存期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.