Loss of lactate dehydrogenase B subunit expression is correlated with tumour progression and independently predicts inferior disease-specific survival in urinary bladder urothelial carcinoma

Aims: In our previous studies, comparative proteomics demonstrated that lactate dehydrogenase B subunit (LDH-B) is down-regulated in high grade compared to non-high grade urinary bladder urothelial carcinoma (UBUC). However, this finding has not been validated by clinical cohort investigation. Therefore, in the present study, 269 primary localised UBUC specimens were examined for LDH-B expression to clarify the relevance of LDH-B expression level to UBUC progression. Methods: Immunohistochemistry (IHC) was implemented to investigate LDH-B protein expression in 269 primary localised UBUC specimens and to evaluate the association with tumour progression and prognosis. Results: Our data demonstrated that dwindled LDH-B expression level was strongly associated with increment of primary tumour status (p < 0.0001), higher histological grade (p = 0.0024), and the presence of vascular (p = 0.0118) as well as perineurial (p = 0.0094) invasion, suggesting that LDH-B might be related to tumour progression. At the univariate level, low LDH-B expression is one of many parameters which significantly predicted both disease-specific survival (DSS) (p = 0.0001) and metastasis-free survival (MeFS) (p = 0.0024). In Cox multivariate regression model, higher pT status was the strongest independent prognosticator for both DSS (p = 0.0006) and MeFS (p = 0.0067) while low LDH-B expression remained prognostically significant for DSS (p = 0.0401). Conclusion: The above results confirmed the prognostic roles of LDH-B in UBUC.