Identification of a robust T cell marker-based gene pair signature for predicting immunotherapy response and prognosis risk in renal cell carcinoma patients

Abstract

Abstract Background Immunotherapy has emerged as an effective approach for improving clinical outcomes in patients with advanced or conventionally drug-resistant cancers. T cells have been recognized as pivotal components in anti-tumor immune activity and the modulation of the tumor microenvironment. However, the precise contributions of T cells in the context of renal cell carcinoma (RCC) remain inadequately understood. Methods Integrated analysis of single-cell and bulk tissue transcriptome profiling was performed to systematically investigate the association between T cells and prognosis and immunotherapy efficacy. By combining the RCC-Braun_2020, TCGA-KIRC and EMATB-1980 cohorts, a novel gene pair index(GPI) for T-cell marker genes was constructed and validated. Moreover, the immune-infiltrating cells of RCC was analyzed using ssGSEA, and the association between GPI and two important immunological factors: cytolytic activity(CYT) and immune checkpoint(ICB) expression levels was investigated. Finally, the function of PRSS23 in RCC was verified. Results The RCC-Braun_2020 cohort suggested that high relative infiltration abundance of T cells was associated with poor clinical outcome and immunotherapy efficacy. GPI possessed a solid ability to predict the prognosis of RCC and T cells with low GPI were significantly associated with immune-related signaling pathways. The immune infiltration results showed that the low-GPI group had significantly higher immune cell infiltration, whereas high-GPI group had higher CYT and ICB. Further, PRSS23 was identified to be involved in metastasis and immunity of RCC, and its significance has been experimentally validated in vitro. Conclusion Overall, a gene pair signature applicable to predict prognosis hopefully provides a reference to guide clinical practice.