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


CONCLUSIONS
The above results confirmed the prognostic roles of LDH-B in UBUC.
Departments of Urology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Alex C
AC
Liao
Chien-Feng
CF
Li
Kun-Hung
KH
Shen
Lan-Hsiang
LH
Chien
Hsuan-Ying
HY
Huang
Ting-Feng
TF
Wu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1