Loss of lactate dehydrogenase B subunit expression is correlated with tumour progression and independently predicts inferior disease-specific survival in urinary bladder urothelial carcinoma
Loss of lactate dehydrogenase B subunit expression is correlated with tumour progression and independently predicts inferior disease-specific survival in urinary bladder urothelial carcinoma
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DOI：
10.1097/pat.0b013e32834bf67a
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发表时间：
2011-12-01
期刊：
影响因子：
4.5
通讯作者：
Wu, Ting-Feng
中科院分区：
文献类型：
--
作者：
Liao, Alex C.;Li, Chien-Feng;Wu, Ting-Feng
目的：在我们之前的研究中，比较蛋白质组学表明，与非高级别膀胱尿路上皮癌 (UBUC) 相比，高级别膀胱尿路上皮癌 (UBUC) 中乳酸脱氢酶 B 亚基 (LDH-B) 下调。然而，这一发现尚未得到临床队列研究的验证。因此，在本研究中，检测了269个原发性局部UBUC标本的LDH-B表达，以阐明LDH-B表达水平与UBUC进展的相关性。方法：采用免疫组织化学（IHC）来研究269个原发性局部UBUC标本中的LDH-B蛋白表达，并评估与肿瘤进展和预后的关系。结果：我们的数据表明，LDH-B表达水平的降低与原发性肿瘤状态的增加密切相关。 (p < 0.0001)、较高的组织学分级 (p = 0.0024) 以及血管 (p = 0.0118) 和神经周围 (p = 0.0094) 侵犯的存在，表明 LDH-B 可能与肿瘤进展有关。在单变量水平上，低 LDH-B 表达是显着预测疾病特异性生存 (DSS) (p = 0.0001) 和无转移生存 (MeFS) (p = 0.0024) 的众多参数之一。在 Cox 多元回归模型中，较高的 pT 状态是 DSS (p = 0.0006) 和 MeFS (p = 0.0067) 最强的独立预后因素，而低 LDH-B 表达对于 DSS 仍具有预后意义 (p = 0.0401)。 结论：上述结果证实了 LDH-B 在 UBUC 中的预后作用。
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.