A novel platelet risk score for stratifing the tumor immunophenotypes, treatment responses and prognosis in bladder carcinoma: results from real-world cohorts

Abstract

Background: Although the durable efficacy of immune checkpoint inhibitors (ICIs) in BLCA has been confirmed in numerous studies, not all patients benefit from their application in the clinic. Platelets are increasingly being found to be closely associated with cancer progression and metastasis; however, their comprehensive role in BLCA remains unclear. Methods: We comprehensively explored platelet expression patterns in BLCA patients using an integrated set of 244 related genes. Correlations between these platelet patterns with tumor microenvironment (TME) subtypes, immune characteristics and immunotherapy efficacies were explored. In addition, a platelet risk score (PRS) was generated for individual prognosis and verified the ability to predict prognosis, precise TME phenotypes, and immunotherapy efficacies. Results: Genes were clustered into two patterns that represented different TME phenotypes and had the ability to predict immunotherapy efficacy. We constructed a PRS that could predict individual prognosis with satisfactory accuracy using TCGA-BLCA. The results remained consistent when PRS was validated in the GSE32894 and Xiangya cohort. Moreover, we found that our PRS was positively related to tumor-infiltrating lymphocytes (TILs) in the TCGA-BLCA and Xiangya cohort. As expected, patients with higher PRS exhibited more sensitive to immunotherapy than patients with lower PRS. Finally, we discovered that a high PRS indicated a basal subtype of BLCA, whereas a low PRS indicated a luminal subtype. Conclusion: Platelet-related genes could predict TME phenotypes in BLCA. We constructed a PRS that could predict the TME, prognosis, immunotherapy efficacy, and molecular subtypes in BLCA.

Keywords: bladder carcinoma; immunotherapy; platelet; prognosis; tumor microenvironment.