Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients.

ABSTRACT

Background: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related lncRNAs as potential biomarkers for prognosis and immunotherapy in GC patients. Methods: We obtained relevant datasets from the Cancer Genome Atlas (TCGA) and Gene Ontology (GO) Resource Database. Pearson correlation analysis was used to identify PLT-related lncRNAs. By using the univariate, least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we constructed the PLT-related lncRNAs model. Kaplan-Meier survival analysis, univariate, multivariate Cox regression analysis, and nomogram were used to verify the model. The Gene Set Enrichment Analysis (GSEA), drug screening, tumor immune microenvironment analysis, epithelial-mesenchymal transition (EMT), and DNA methylation regulators correlation analysis were performed in the high- and low-risk groups. Patients were regrouped based on the risk model, and candidate compounds and immunotherapeutic responses aimed at GC subgroups were also identified. The expression of seven PLT-related lncRNAs was validated in clinical medical samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: In this study, a risk prediction model was established using seven PLT-related lncRNAs -(AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, and AL356417.2), whose expression were validated in GC patients. Kaplan-Meier survival analysis, the receiver operating characteristic (ROC) curve analysis, univariate, multivariate Cox regression analysis verified the accuracy of the model. We screened multiple targeted drugs for the high-risk patients. Patients in the high-risk group had a poorer prognosis since low infiltration of immune killer cells, activation of immunosuppressive pathways, and poor response to immunotherapy. In addition, we revealed a close relationship between risk scores and EMT and DNA methylation regulators. The nomogram based on risk score suggested a good ability to predict prognosis and high clinical benefits. Conclusion: Our findings provide new insights into how PLT-related lncRNAs biomarkers affect prognosis and immunotherapy. Also, these lncRNAs may become potential biomarkers and therapeutic targets for GC patients.