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

Tumour Biol. 2017 Mar;39(3):1010428317695968. doi: 10.1177/1010428317695968.

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.

Keywords: Lactate dehydrogenase C; cancer–testis antigens; epithelial–mesenchymal transition; renal cell carcinoma; tumour metastasis.

MeSH terms

  • Adult
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • L-Lactate Dehydrogenase / biosynthesis*
  • L-Lactate Dehydrogenase / genetics
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Isoenzymes
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase C4
  • MMP9 protein, human
  • Matrix Metalloproteinase 9