HYAL3 as a potential novel marker of BLCA patient prognosis

Abstract

Background: It has been previously demonstrated that hyaluronan (HA) potentially regulates the initiation and propagation of bladder cancer (BLCA). HYAL3 encodes hyaluronidase and is a potential therapeutic target for BLCA. We aimed to explore the role that HYAL3 plays in BLCA pathogenesis.

Methods: HYAL3 expression in BLCA specimens was analyzed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) cohort as well as confirmed in cell lines and The Human Protein Atlas. Then, associations between HYAL3 expression and clinicopathological data were analyzed using survival curves and receiver-operating characteristic (ROC) curves. The functions of HYAL3 were further dissected using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the protein-protein interaction network. Finally, we harnessed the Tumor IMmune Estimation Resource and Gene Expression Profiling Interactive Analysis to obtain correlations between HYAL3 expression, infiltrating immunocytes, and the corresponding immune marker sets.

Results: HYAL3 expression varied greatly between many types of cancers. In addition, a higher HYAL3 expression level predicted a poor overall survival (OS) in both TCGA-BLCA and GEO gene chips (P < 0.05). HYAL3 also exhibited an acceptable diagnostic ability for the pathological stage of BLCA (area under the receiver-operating characteristic curve = 0.769). Furthermore, HYAL3 acted as an independent prognostic factor in BLCA patients and correlated with the infiltration of various types of immunocytes, including B cells, CD8⁺ T cells, cytotoxic cells, T follicular helper cells, and T helper (Th) 2 cells.

Conclusion: HYAL3 might serve as a potential biomarker for predicting poor OS in BLCA patients and correlated with immunocyte infiltration in BLCA.

Keywords: Bioinformatic analysis; Bladder cancer; HYAL3; Immune cells; TCGA.