A novel platelets-related gene signature for predicting prognosis, immune features and drug sensitivity in gastric cancer
Background: Platelets play a dynamic role in regulating tumor development and progression, but their specific contributions and predictive value in gastric cancer (GC) remain poorly understood. This study aims to establish a platelet-related gene signature in GC with potential prognostic and therapeutic implications.
Methods: Transcriptome data and clinical information from 378 GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Prognostic platelet-related genes were identified through univariate Cox regression analysis and subjected to Least Absolute Shrinkage and Selection Operator (LASSO) analysis to develop a risk model. The model’s predictive performance was assessed using Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves in the TCGA cohort and three independent validation cohorts. A nomogram incorporating the risk score and clinicopathological features was also constructed. Functional enrichment and tumor microenvironment (TME) analyses were conducted, and drug sensitivity predictions were made using The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR).
Results: A ten-gene predictive risk model, consisting of SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF, was developed. Patients were stratified into high- and low-risk groups based on the median risk score. The area under the ROC curve (AUC) for 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis demonstrated significantly better OS in low-risk patients across both training and validation cohorts. The nomogram’s AUCs for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analysis revealed higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Additionally, high-risk patients showed increased sensitivity to thalidomide, MK-0752, and BRD-K17060750.
Conclusion: The novel platelet-related gene signature identified in this study holds potential for prognostic prediction and treatment response in GC.