Expression of lactate/H+ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma: Immunohistochemical and the Cancer Genome Atlas data analyses

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Abstract

Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4% (89/180), 39.4% (71/180), and 79.4% (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P =.017), larger tumor size (P =.015), and advanced TNM stage (P =.012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P =.005), tumor necrosis (P =.016), and larger tumor size (P =.038). In univariate analysis, high expression of MCT1 (P <.001), MCT4 (P =.016), and CD147 (P =.02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P =.001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalHuman Pathology
Volume46
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Symporters
Atlases
Renal Cell Carcinoma
Lactic Acid
Genome
Neoplasms
Disease-Free Survival
Monocarboxylic Acid Transporters
Hypoxia-Inducible Factor 1
Oncogene Proteins
Glycolysis
Cell Survival
Necrosis
Multivariate Analysis
Immunohistochemistry
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{8fa26445ba8e4d9593274ec2929ed847,
title = "Expression of lactate/H+ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma: Immunohistochemical and the Cancer Genome Atlas data analyses",
abstract = "Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4{\%} (89/180), 39.4{\%} (71/180), and 79.4{\%} (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P =.017), larger tumor size (P =.015), and advanced TNM stage (P =.012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P =.005), tumor necrosis (P =.016), and larger tumor size (P =.038). In univariate analysis, high expression of MCT1 (P <.001), MCT4 (P =.016), and CD147 (P =.02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P =.001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression.",
keywords = "Aerobic glycolysis, CD147, Monocarboxylate, Renal cell carcinoma, TCGA",
author = "Younghye Kim and Jung-Woo Choi and Ju-Han Lee and Kim, {Young Sik}",
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doi = "10.1016/j.humpath.2014.09.013",
language = "English",
volume = "46",
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journal = "Human Pathology",
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T1 - Expression of lactate/H+ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma

T2 - Immunohistochemical and the Cancer Genome Atlas data analyses

AU - Kim, Younghye

AU - Choi, Jung-Woo

AU - Lee, Ju-Han

AU - Kim, Young Sik

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4% (89/180), 39.4% (71/180), and 79.4% (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P =.017), larger tumor size (P =.015), and advanced TNM stage (P =.012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P =.005), tumor necrosis (P =.016), and larger tumor size (P =.038). In univariate analysis, high expression of MCT1 (P <.001), MCT4 (P =.016), and CD147 (P =.02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P =.001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression.

AB - Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4% (89/180), 39.4% (71/180), and 79.4% (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P =.017), larger tumor size (P =.015), and advanced TNM stage (P =.012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P =.005), tumor necrosis (P =.016), and larger tumor size (P =.038). In univariate analysis, high expression of MCT1 (P <.001), MCT4 (P =.016), and CD147 (P =.02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P =.001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression.

KW - Aerobic glycolysis

KW - CD147

KW - Monocarboxylate

KW - Renal cell carcinoma

KW - TCGA

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