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Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.

ABSTRACT: Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords "cancer", "Monocarboxylate transporter 1", "SLC16A1" and "prognosis". Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter's overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.

SUBMITTER: Silva A

PROVIDER: S-EPMC10049181 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.

Silva Ana A Cerqueira Mónica Costa MC Rosa Beatriz B Sobral Catarina C Pinto-Ribeiro Filipa F Costa Marta Freitas MF Baltazar Fátima F Afonso Julieta J

International journal of molecular sciences 20230307 6

Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different ma ...[more]

PMID: 36982217

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Project description:BackgroundHigh mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study.MethodsUsing The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer.ResultsPan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma.ConclusionBreast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Project description:BackgroundTumor hypoxia plays a fundamental role in resistance to therapy and disease progression. A number of studies have assessed the prognostic role of HIFs expression in head and neck cancer (HNC), but no consistent outcomes are reported.MethodologyA systematical search was performed to search relevant literatures in PubMed, Web of Science and ISI Web of Knowledge databases. The patients' clinical characteristics and survival outcome were extracted. The correlation between HIFs expression and prognosis was analyzed.Principal findingsA total of 28 studies assessed the association between HIFs and HNC survival, the result showed that overexpressed HIFs was significantly associated with increase of mortality risk (HR = 2.12; 95% CI: 1.52-2.94; I(2) 74%). Subgroup analysis on different HIF isoforms with OS indicated that both HIF-1α and HIF-2α were associated with worse prognosis. The pooled HRs were 1.72(95% CI 1.34-2.20; I(2) 70.7%) and 1.79(95% CI: 1.42-2.27, I(2) 0%). Further subgroup analysis was performed by different geographical locations, disease subtype, stage, types of variate analysis and cut-off value. The results revealed that overexpressed HIF-1α was significantly associated with poor prognosis in Asian patients (HR = 2.34; 95% CI: 1.76-3.1; I(2) 48.9%), but not in European patients (HR = 1.13; 95% CI: 0.77-1.66; I(2) 78.3%). Furthermore, HIF-1α overexpression was significantly associated with worse OS in oral carcinoma (HR = 2.1; 95% CI: 1.11-3.97; I(2) 81.7%), nasopharyngeal carcinoma (HR = 2.07; 95% CI:1.23-3.49; I(2) 22.5%) and oropharynx carcinoma (HR = 1.76; 95% CI:1.05-2.97; I(2) 61%), but not in laryngeal carcinoma (HR = 1.38; 95% CI: 0.87-2.19; I(2) 62.5%). We also found that the prognostic value of HIF-1α overexpression existed only when using staining and percentage as positive definition (HR = 1.82; 95% CI 1.42-2.33; I(2) 9.9%).ConclusionsThis study showed that overexpressed HIFs were significantly associated with increase of mortality risk. Subgroup analysis revealed that overexpressed HIF-1α was significantly associated with worse prognosis of HNC in Asian countries. Additionally, HIF-1α had different prognostic value in different HNC disease subtypes.

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Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.

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Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.

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