WCLC 2025 - Posters & ePosters-P1.04.30 Screening of Paraptosis-Related Prognostic Genes in Lung Adenocarcinoma By Bioinformatics Analysis and Experimental Validation

P1.04.30 Screening of Paraptosis-Related Prognostic Genes in Lung Adenocarcinoma By Bioinformatics Analysis and Experimental Validation

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This study investigates the prognostic significance of paraptosis-related genes (PRGs) in lung adenocarcinoma (LUAD) through bioinformatics analyses and experimental validation. Paraptosis is a form of programmed cell death whose role in LUAD remains not fully elucidated. Researchers identified differentially expressed genes (DEGs) in LUAD patient data sets, intersected these with known PRGs to obtain candidate genes (CGs), and applied regression analyses to screen four key prognostic genes: CDKN3, PEBP1, TNFRSF19, and PHB.<br /><br />A prognostic risk model incorporating these genes was developed and validated in independent cohorts, showing robust predictive capability for LUAD survival outcomes. Risk scores derived from this model correlated significantly with clinical features including age, TNM stage, T stage, and N stage, serving as independent prognostic factors. A nomogram combining risk scores with clinical factors effectively predicted 1-, 3-, and 5-year survival probabilities. Functional analyses revealed that high- and low-risk patient groups exhibited distinct biological pathways such as spindle elongation and varied immune cell infiltration patterns, suggesting PRGs affect tumor microenvironment and immune responses.<br /><br />Molecular docking identified vorinostat and raloxifene as drugs with strong binding affinity to PEBP1, indicating potential therapeutic applications. PCR validation confirmed elevated CDKN3 expression and decreased PEBP1 and TNFRSF19 expression in LUAD tissues.<br /><br />Conclusions highlight CDKN3 and PHB as risk factors impacting prognosis, whereas PEBP1 and TNFRSF19 showed protective trends. The study provides insights into PRGs' prognostic value, tumor immunity interactions, and drug targeting potential, though some immune correlations require further investigation.<br /><br />Future work aims to refine the prognostic model by including more genes, clinical variables, and staging details, and to validate findings across larger, multicenter cohorts using RT-qPCR. Overall, this research advances understanding of paraptosis-related mechanisms in LUAD and aids development of improved prognostic tools and therapeutic strategies.

Asset Subtitle

Tao Zhang

Meta Tag

Speaker Tao Zhang

Topic Screening and Early Detection

Keywords

paraptosis

lung adenocarcinoma

prognostic model

CDKN3

PEBP1

TNFRSF19

PHB

tumor microenvironment

immune infiltration

molecular docking