Identification and validation of crotonylation-related diagnostic markers for lung adenocarcinoma via weighted correlation network analysis and machine learning.
Bowen Hu, Xin Chen, Dan Zou, Xiaoyue Du, Sitong Feng, Yiwen Shen, Xiaofeng Sha, Feng Jiang, Guoren Zhou, Fan Lin, Lukas Käsmann, Bo Shen
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引用次数: 0
Abstract
Background: Lung adenocarcinoma (LUAD) is one of the most common tumors in terms of incidence and mortality worldwide. Posttranslational modifications, including crotonylation, play a crucial role in various biological processes and diseases. However, the role of crotonylation in LUAD remains unclear. Our research focuses on identifying key genes in LUAD that are linked to crotonylation and prognosis. We also aim to clarify their role in the LUAD microenvironment to advance clinical translation of related targets.
Methods: We used RNA-sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to identify differentially expressed genes (DEGs) related to crotonylation in LUAD. Weighted correlation network analysis (WGCNA) was applied to construct gene networks, and hub genes were identified using protein-protein interaction (PPI) analysis. The prognostic value of hub genes was assessed using Kaplan-Meier plots, and the correlation with immune infiltration was analyzed via Tumor Immune Estimation Resource (TIMER) and other algorithms. We then verified these genes through clinical samples and confirmed the role of MMACHC in LUAD.
Results: We identified GAPDH, SLC25A13, MMACHC, and HDAC1 as potential crotonylation-related biomarkers for LUAD. These genes were found to be overexpressed in LUAD and were associated with poor prognosis. They also showed significant correlations with immune cell infiltration and immune-inflammatory pathways. Functional experiments confirmed that MMACHC knockdown inhibited cell proliferation and migration, induced apoptosis, and enhanced the efficacy of immunotherapy in LUAD.
Conclusions: Our study suggests that crotonylation-related genes, particularly MMACHC, may serve as novel therapeutic targets and diagnostic markers for LUAD.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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