P4HB: A novel diagnostic and prognostic biomarker for bladder carcinoma

Abstract

Prolyl 4-hydroxylase, beta polypeptide (P4HB) protein is an endoplasmic reticulum (ER) molecular chaperone protein and has been reported to be overexpressed in multiple tumor types. However, the role of P4HB in bladder cancer (BLCA) has not yet been elucidated. The aim of the present study was to investigate the prognostic value of P4HB and the association between clinicopathological characteristics and P4HB in BLCA. P4HB expression levels were assessed through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis in BLCA tissues and cells. A total of 69 pairs of tumor and normal samples were used to analyze the expression of P4HB via immunohistochemical staining. A co-expression network and functional enrichment analyses were conducted to investigate the biological function of P4HB in BLCA. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes. The results showed that P4HB was highly expressed in BLCA cells and tissues. The area under the curve value for P4HB expression to discriminate between tumor and normal tissues was up to 0.888 (95% CI: 0.801–0.975; P<0.001) and 0.881 (95% CI: 0.825–0.937; P<0.001) in TCGA database and our database, respectively. Furthermore, the expression level of P4HB was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) by univariate and multivariate analyses. Kaplan-Meier survival analysis demonstrated that high P4HB expression was associated with low OS and RFS. Pathway enrichment analysis suggested that P4HB was involved in protein processing in the endoplasmic reticulum (ER), including N-glycan modification and protein metabolic processes responding to ER stress. PPI analysis revealed that the potential targets of P4HB were mainly involved in posttranslational protein modification and response to ER stress. In conclusion, the expression level of P4HB aid in identifying patients with early-stage BLCA and predicting the prognosis of BLCA. Therefore, P4HB may be a novel diagnostic and prognostic biomarker for BLCA.

An Unfolded Protein Response Related Signature Could Robustly Predict Survival Outcomes and Closely Correlate With Response to Immunotherapy and Chemotherapy in Bladder Cancer

“…Due to the significance of UPR in tumors, many researchers have paid more attention to UPR related biomarkers. It has been reported that OTUB1, P4HB, and EHMT2 could regulate the malignant phenotype of bladder cancer cells via the ERS related URP pathway ( Cui et al, 2015 ; Wang et al, 2020 ; Zhang et al, 2021c ; Wu et al, 2021 ).…”

High expression of transmembrane P24 trafficking protein 9 predicts poor prognosis in breast carcinoma

“…On the other hand, PPIB, a peptidylpropyl isomerase, participated in colorectal cancer progression and chemoresistance [49]. Studies have also suggested that P4HB may extensively regulate tumor progression and prognosis of patients with cancer [50][51][52][53][54], including BRCA [55,56]. In BRCA, TMED9 may affect cancer progression and prognosis by interacting with these proteins.…”

Gene Co-Expression Network Analysis Confirms Four Independent Predictors of Survival In Ovarian Cancer Patients Under Optimal Debulking Surgery

“…Autophagy-related gene prolyl 4-hydroxylae, beta polypeptide (P4HB) has been validated as a promising diagnosis and prognosis biomarker in kidney renal clear cell carcinoma [21] and bladder cancer [22]. Besides, P4HB contributes to cell proliferation, migration or invasion in gastric cancer [23], breast cancer [24] and colon cancer [25] through multiple pathways.…”