Comprehensive pan-cancer analysis indicates UCHL5 as a novel cancer biomarker and promotes cervical cancer progression through the Wnt signaling pathway.

Background: UCHL5 was initially recognized as a multifunctional molecule. While recent research has highlighted its involvement in tumor malignant biological behaviors, its specific role in promoting tumor cell apoptosis has drawn particular attention. However, the precise relationship between UCHL5 and various tumor types, as well as its influence within the immune microenvironment, remains unclear.

Methods: The transcriptomic data and clinicopathological parameters across 33 cancer types were obtained from TCGA. Clinical pathological parameters of tumor patients, including gender, age, survival time, and staging, are utilized to evaluate the association between UCHL5 and pan-cancer characteristics. The prognostic significance of UCHL5 was evaluated through Cox analysis and Kaplan-Meier (K-M) methods. Protein expression data for UCHL5 were obtained from The Human Protein Atlas database, and its subcellular localization was further investigated. Additionally, potential correlations between UCHL5 and factors such as tumor-infiltrating immune cells, immunomodulators, microsatellite instability (MSI), and tumor mutation burden (TMB) were explored. The relationship between UCHL5 and immunotherapy efficacy was also assessed in independent cohorts, including IMvigor210, GSE78220, GSE67501, and GSE168204. Finally, the impact of UCHL5 on the malignant biological behavior of cervical cancer cells was investigated through in vitro experiments, along with an exploration of the underlying mechanisms.

Results: We observed that UCHL5 expression levels were elevated in 11 types of cancer tissues compared to their corresponding normal tissues, while levels were lower in five tumor types. Additionally, UCHL5 expression displayed a significant correlation with tumor stage in BRCA, KIRC, LUAD, and TGCT. Cox and K-M analysis indicated that UCHL5 expression was significantly associated with prognosis in KIRC, KICH, CESC, ACC, and UVM. UCHL5 expression was negatively associated with stromal and immune scores in certain cancers. In terms of immune cell infiltration, UCHL5 expression in UCEC, SKCM, and COAD showed a negative correlation with regulatory T cells (Tregs). Furthermore, UCHL5 was widely associated with three types of immunomodulators. It also demonstrated a significant relationship with MSI and TMB in certain cancers and was connected to the immunotherapy efficacy. Finally, in vitro experiments confirmed that UCHL5 knockout enhances apoptosis in cervical cancer cells and disrupts Wnt/β-catenin signaling.

Conclusions: Pan-cancer analysis indicates that UCHL5 is dysregulated in various tumor tissues and is closely associated with survival prognosis, the tumor immune microenvironment, and the efficacy of immunotherapy in certain cancer types. UCHL5 shows promise as a predictive biomarker, and its specific regulatory mechanisms across different cancers warrant further investigation.