Identification of Progression-Associated Biomarkers in Lung Cancer Based on the Integrated Analysis of RNA Sequencing...

Objective: This study is aimed at exploring disease progression-associated genes from platelet-derived genes and at investigating their underlying roles in prognostic outcomes in lung cancer. Methods: Platelet RNA sequencing (RNA-seq) from healthy controls (n = 81) and lung cancer patients at early (n = 102) and advanced stages (n = 65) was conducted, and the genes from which that continuously changed with disease progression were screened by differential analysis and WGCNA. RNA-seq and survival data of LUAD cohort from TCGA database was utilized for prognostic investigation. GSE31210 and GSE18842 datasets from GEO database were utilized for validation of gene expression and prognosis. The immunedeconv package and ESTIMATE algorithm were employed for investigation of immune status. Gene mutation was evaluated based on the cBioPortal database. Drug sensitivity was assessed based on the GDSC database. Results: Totally, 53 platelet-derived genes that were persistently dysregulated along with the progression from normal to early and then advanced were identified. These 53 genes were primarily enriched in ribosome biogenesis-related functions. Five prognostic genes, including HPSE, DENND1C, GRWD1, HLA-DQA1, and PDXK, were identified to further develop a risk signature, which exhibited moderate power for forecasting the prognosis of lung cancer patients in training, testing, and validation sets. In addition, a high-risk signature score was linked to low infiltrating levels of most immune cells and a high tumor purity in the tumor microenvironment, as well as low IC50 values to several common chemotherapeutics, such as docetaxel, gefitinib, and erlotinib. Moreover, energy metabolism and proliferation-related pathways were activated, while immune-related pathways were inactivated in the high-risk group. Among the five prognostic genes, HLA-DQA1 harbored a relatively higher alteration frequency in LUAD (3%, alteration type: amplification). Conclusion: The five platelet-derived prognostic genes might be potential targets or biomarkers in lung cancer.