Prognostic impact and immunotherapeutic implications of NETosis-related prognostic model in clear cell renal cell carcinoma.

ABSTRACT

BACKGROUND: The ramifications of necroptosis on the prognostication of clear cell renal cell carcinoma (ccRCC) remain inadequately expounded. METHODS: A prognostic model delineating the facets of necroptosis in ccRCC was constructed, employing a compendium of algorithms. External validation was effectuated using the E-MTAB-1980 dataset. The exploration of immune infiltration scores was undertaken through the exploitation of multiple algorithms. Single-cell RNA sequencing data were procured from the GSE171306 dataset. Real-time quantitative PCR (RT-qPCR) was engaged to scrutinize the differential expression of SLC25A37 across cancer and paracancer tissues, as well as diverse cell lines. Assessments of proliferative and metastatic alterations in 769-P and 786-O cells were accomplished through Cell Counting Kit-8 (CCK8) and wound healing assays. RESULTS: The necroptosis-related signature (NRS) emerges as a discerning metric, delineating patients' immune attributes, tumor mutation burden, immunotherapy response, and drug susceptibility. Single-cell RNA sequencing analysis unveils the marked enrichment of SLC25A37 in tumor cells. Concurrently, RT-qPCR discloses the overexpression of SLC25A37 in both ccRCC tissues and cell lines. SLC25A37 knockdown mitigates the proliferative and metastatic propensities of 769-P and 786-O cells, as evidenced by CCK8 and wound healing assays. CONCLUSION: The NRS assumes a pivotal role in ascertaining the prognosis, tumor mutation burden, immunotherapy response, drug susceptibility, and immune cell infiltration features of ccRCC patients. SLC25A37 emerges as a putative player in immunosuppressive microenvironments, thereby providing a prospective avenue for the design of innovative immunotherapeutic targets for ccRCC.