Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma

Abstract

Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma. KeywordsLactate dehydrogenase C, cancer-testis antigens, renal cell carcinoma, tumour metastasis, epithelial-mesenchymal transition Date received: 20 September 2016; accepted: 23 December 2016 1 Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China 2 Department of Pathology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China Corresponding authors:Zengjun Wang, Department of Urology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Email: 13913962589@163.com Chao Qin, Department of Urology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Email: urology_qinchao@163.com 695968T UB0010.1177/1010428317695968Tumor BiologyHua et al. research-article2017Original Article 2 Tumor Biology the testis and in various malignant tumours, which are silenced in the somatic tissues. 3 Recent articles have proposed that CTAs play critical roles in various malignant cancer cells. 4 Because of these specific characters, CTAs are considered promising targets for early diagnosis and immunotherapy for cancers. However, the potential that RCC patients might benefit from CTA-targeted therapies remains to be evaluated.Lactate dehydrogenase (LDH) is an important glycolytic enzyme that catalyses the transition of pyruvate to l-lactate in the glycolytic pathway. 5 LDH family includes three isoenzymes, namel...

Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy

“…In addition, increased LDHA and decreased LDHB expressions facilitate tumor formation and progression through remodeling of the tumor microenvironment, increasing proliferation, and inducing epithelial-to-mesenchymal transition, cell migration and invasion, and angiogenesis [10][11][12][13][14][15][16][17][18][19][20]. In line with this, two studies to date demonstrate that enhanced expression of LDHC induces epithelial-to-mesenchymal transition, matrix metalloproteinase-9 (MMP9) expression and promotes cancer cell migration and invasion [7,21].…”

“…Although LDHC expression is tightly controlled and suppressed in normal somatic tissues, it is re-expressed in various malignant tissues, making its expression highly tumor specific [6]. Furthermore, increased LDHC expression has been associated with poor prognosis in renal cell carcinoma [7]. Very little data are available on the role of LDHC in cancer.…”

Prognostic Value of Lactate Dehydrogenase Expression in Different Cancers: A Meta-Analysis

“…It plays an important function in maintaining glycolysis and producing adenosine triphosphate, which is essential for spermatogenesis. 7 LDHD is also a tumorrelated gene. However, studies on it are limited.…”

Development of a novel nomogram for the prediction of cause specific survival for patients with non-metastatic Chromophobe Cell Renal Carcinoma, following radical nephrectomy

“…First, our model was built from the data contained in the SEER database, therefore its accuracy is directly linked to the accuracy of data collection and input into that database. Secondly, in the development of the nomogram, we included only clinical and histological parameters, but there are other biochemical parameters, such as the serum level of lactic acid dehydrogenase (LDH), that might also be associated with adverse pathological features and that could be related to oncological outcomes [27]. Moreover, postoperative adjuvant therapy is also a major factor in uencing the prognosis of the disease, however none of these variables were included in the present model because they were not available for the patients that were included in the study.…”