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Prognostic and predictive value of monocarboxylate transporter 4 in patients with breast cancer.

ABSTRACT: The Warburg effect explains the large amount of lactic acid that tumour cells produce to establish and maintain the acidic characteristics of the tumour microenvironment, which contributes to the migration, invasion and angiogenesis of tumour cells. Monocarboxylate transporter 4 (MCT-4) is a key marker of tumour glycolysis and lactic acid production; however, the role of MCT-4 in breast cancer remains unclear. In the present study, immunohistochemistry (IHC) was used to detect the expression levels of MCT-4 in tissue microarrays of 145 patients diagnosed with invasive ductal breast cancer. The IHC score was used to assess the intensity of staining and the proportion of positive cells. Western blotting and reverse transcription-quantitative PCR were also performed to detect the expression levels of MCT-4 in 30 pairs of breast cancer tissues and adjacent normal tissues. In vitro experiments (EdU incoporation and Cell Counting Kit-8) were performed to examine the role of MCT-4 in the breast cancer MCF-7 cell line. The results of the present study indicated that high MCT-4 expression was associated with pT status (P=0.018), oestrogen receptor (ER) status (P=0.001), progesterone receptor (PR) status (P=0.024), Ki67 index (P=0.043) and androgen receptor (AR) status (P=0.033). In addition, an association between MCT-4 expression and pathological grade was observed (P=0.030). Furthermore, univariate (P=0.027) and multivariate (P=0.001) survival analysis revealed that MCT-4 expression and lymph node involvement were significant independent predictors of breast cancer prognosis. In addition, silencing MCT-4 expression attenuated breast cancer cell viability. Therefore, MCT-4 may be used as a potential predictor of invasive breast cancer.

SUBMITTER: Xiao S

PROVIDER: S-EPMC7400967 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prognostic and predictive value of monocarboxylate transporter 4 in patients with breast cancer.

Xiao Sheng S Zhu Hongjia H Shi Yujun Y Wu Zhenru Z Wu Hegang H Xie Mingjun M

Oncology letters 20200625 3

The Warburg effect explains the large amount of lactic acid that tumour cells produce to establish and maintain the acidic characteristics of the tumour microenvironment, which contributes to the migration, invasion and angiogenesis of tumour cells. Monocarboxylate transporter 4 (MCT-4) is a key marker of tumour glycolysis and lactic acid production; however, the role of MCT-4 in breast cancer remains unclear. In the present study, immunohistochemistry (IHC) was used to detect the expression lev ...[more]

PMID: 32782531

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Project description:BackgroundZinc finger E-box binding homeobox 1 (ZEB1) is a molecule involved in the progression of epithelial-to-mesenchymal transition (EMT) in various kinds of cancers. Here, we aimed to determine whether the expression of the ZEB1 protein is related to the response of patients to neoadjuvant therapy as well as their survival outcome.MethodsImmunohistochemistry (IHC) was performed on paraffin-embedded tumor samples from core needle biopsy before neoadjuvant therapy (NAT). Univariate and multivariate logistic regression analyses were used to analyze the associations between the protein expression of ZEB1 and the pathological complete response (pCR) outcome. Kaplan-Meier plots and log-rank tests were used to compare disease-free survival (DFS) between groups. A Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidential interval (95% CI).ResultsA total of 75 patients were included in the IHC test. High ZEB1 protein expression was associated with a low pCR rate in both univariate (OR = 0.260, 95% CI 0.082-0.829, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011-0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024-79.519, p = 0.048). In hormone receptor positive (HorR-positive) patients, high ZEB1 protein expression was also associated with a lower pCR (OR = 0.054, 95% CI 0.007-0.422, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171-94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 0.042).ConclusionsOur results showed that high ZEB1 protein expression was a negative predictive marker of pCR and DFS in neoadjuvant therapy in breast cancer patients and in HorR-positive and HER2-overexpressing subgroups.Trial registration NCT, NCT02199418. Registered 24 July 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1. NCT, NCT 02221999. Registered 21 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1.

Dataset Information

Prognostic and predictive value of monocarboxylate transporter 4 in patients with breast cancer.

Publications

Prognostic and predictive value of monocarboxylate transporter 4 in patients with breast cancer.

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