Multi-cancer profiling and breast cancer validation reveal YME1L1 as a potential immune-related factor and prognostic biomarker

Mitochondrial dysfunction constitutes a fundamental driver of neoplastic transformation. YME1L1, an inner mitochondrial membrane-resident AAA+ metalloprotease, is associated with protein homeostasis in the inner mitochondrial membrane and intermembrane space, thus participating in cellular metabolic reprogramming. Nevertheless, systematic interrogation of YME1L1 across Multiple cancers remains conspicuously absent. We harnessed public repositories including TCGA, GTEx, GEO, HPA, cBioPortal, and GSCA to comprehensively delineate YME1L1 expression landscapes, prognostic implications, diagnostic performance, genomic alteration patterns, and predicted immuno-oncological correlations across diverse malignancies via bioinformatics. Subsequent in vitro assays and BALB/c nude xenograft models verified cell-intrinsic oncogenic phenotypes of YME1L1. YME1L1 was notably upregulated in most solid carcinomas, with its amplified expression consistently predicting inferior patient outcomes. YME1L1 transcript levels were significantly correlated with TMB, MSI and HRD, well-known molecular markers related to immunotherapy response, suggesting a potential multidimensional association between YME1L1 expression and tumor immune characteristics. Functional enrichment analysis revealed that genes correlated with YME1L1 were enriched in ribonucleoprotein complex biogenesis, mitochondrial translation, and multiple pro-tumorigenic signaling cascades such as the Wnt and Hippo pathways ; however, direct regulation of these pathways by YME1L1 was not experimentally validated. In BRCA specimens, YME1L1 expression markedly exceeded that of normal mammary counterparts. Experimental manipulation suggests that elevated YME1L1 expression may contribute to enhanced proliferative capacity, clonogenic potential, migratory behavior, and invasive properties of breast cancer cells; xenograft studies further corroborated that YME1L1 overexpression accelerated subcutaneous tumor growth, whereas its knock down effectively restrained neoplastic proliferation. Of note, nude mice lack mature T cells and cannot confirm these predicted immune phenotypes. Through multi-tumor profiling coupled with breast cancer functional validation, this investigation reveal YME1L1 as a predicted immune-related influencing factor and therapeutic target, .Our data underscore YME1L1’s clinical relevance and its promise as a novel therapeutic target for various cancers.