Methylated DNA Damage Repair Genes: RRM2 and GAPDH are Prognostic Biomarkers and Correlate with Immunotherapy in Lung Adenocarcinoma
Background: Mounting evidence indicated that aberrant DNA methylation is particularly important in the pathogenesis of lung adenocarcinoma (LUAD). Systematic screening of methylated DNA damage-repair-related genes (DDRGs) with a bioinformatic approach can establish methylated DDRGs-based prognostic...
| Main Authors: | , , , |
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| Format: | Thesis |
| Language: | English English English |
| Published: |
Genetics and Molecular Biology
2025
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| Subjects: | |
| Online Access: | http://ir.unimas.my/id/eprint/50060/ |
| Abstract | Abstract here |
| Summary: | Background: Mounting evidence indicated that aberrant DNA methylation is particularly important in the pathogenesis of lung adenocarcinoma (LUAD). Systematic screening of methylated DNA damage-repair-related genes (DDRGs) with a bioinformatic approach can establish methylated DDRGs-based prognostic biomarker. Nevertheless, limited previous studies identity methylated DDRGs as prognostic biomarker. In this study, the aim was to assess the prognostic value of methylated DDRGs in LUAD.
Methods: LUAD-related datasets were obtained from public databases. In the TCGA-LUAD dataset, differential expression analysis was used to identify differentially expressed genes (DEGs) and differentially expressed methylated genes (DE-MGs). Next, methylated DE-DDRGs were identified by combining up-regulated DEGs with demethylated DE-MGs as well as down-regulated DEGs with hypermethylated DE-MGs. Then, univariate and multivariate cox analyses were done using methylated DE-DDRGs to identify prognostic biomarkers and build risk-prognostic models. Independent prognostic analysis was performed using risk scores and clinical features to identify independent prognostic parameters for nomogram development. Finally, the study examined response to immunotherapy responses.
Results: One high-confidence gene, CLU, was hypermethylated and hyperexpressed in LUAD tissues. In addition, eight hypomethylated and highly expressed genes have been identified (BUB1B, SHCBP1, RRM2, RPL39L, TRIP13, GAPDH, ENO1, and CENPM). Among them, RRM2 and GAPDH were identified by univariate and multivariate analyses as significantly associated with shorter overall survival. Meanwhile, the risk score based on the prognostic signature was also identified as an independent prognostic factor for LUAD.Moreover, the high-risk group associated with the poor prognosis of LUAD showed lower immune/stromal scores and immune infiltration characteristics. Ultimately, TIDE, a tool to predict immunotherapy response, analysis revealed that patients in the low-risk group may be more sensitive to immune checkpoint inhibitor therapy.
Conclusion: RRM2 and GAPDH could serve as promising prognostic and immunotherapeutic biomarkers in LUAD and can contribute to novel drug strategy for LUAD treatment. |
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