High carboxypeptidase E expression correlates with poor bladder cancer survival: retrospective multi-omics and in vitro analysis

Bladder cancer (BLCA) is the second most common genitourinary malignancy worldwide, and its prognosis is poor. Carboxypeptidase E (CPE) enzyme plays a vital role in regulating biosynthesis and has been associated with cancer. However, the prognostic roles of CPE in bladder cancer have not been documented so far. The expression status, potential molecular mechanism, and prognostic value of CPE in BLCA were investigated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, its biological roles in BLCA were explored through in vitro studies. By analyzing data from the TCGA and the GEO databases, we discovered that patients with a high level of CPE had a worse overall prognosis from TCGA BLCA cohort. Furthermore, CPE was identified as an independent risk factor for survival of BLCA patients. These findings suggest a potential association between CPE expression and prognosis of BLCA patients. The underlying biological mechanism may involve CPE’s influence on epithelial–mesenchymal transition (EMT) and the tumor microenvironment (TME). An in vitro study revealed that CPE knockdown inhibited BLCA cell proliferation and growth. Our multi-omics and functional assays link high CPE expression to poorer survival and signatures of EMT and immune exhaustion in bladder cancer, positioning CPE as a candidate prognostic marker for prospective validation.