MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

Javaeed, Arslaan; Ghauri, Sanniya Khan

doi:10.4081/oncol.2019.403

“…Indeed, we observed that the expression of MCT4 was the highest among the four lactate transporters (Supplementary Fig. S1 ) and high expression of MCT4 was associated with poor prognosis in BLCA (HR 1.43, p = 0.02), CESC (HR 2.0, p = 0.01), LIHC (HR 1.9, p = 6e−4) and LUAD (HR 1.83, p = 8e−5), corroborating previous data 24 ⁠. MCT-4 is also the transporhat was identified to regulate glycolytic flux 15 ⁠.…”

Section: Resultssupporting

confidence: 90%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Sci Rep

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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…MCT-4 is considered to be particularly suited for the export of lactate from highly glycolytic cells; additionally, MCT-4 has low a nity for pyruvate, suggesting this transporter to be particularly suited for cancer cells that are known to exhibit high NAD+/NADH ratio 23 . Indeed, we observed that the expression of MCT4 was the highest among the four lactate transporters (Supplementary Figure 1) and high expression of MCT4 was associated with poor prognosis in BLCA (HR 1.43, p=0.02), CESC (HR 2.0, p = 0.01), LIHC (HR 1.9, p=6e-4) and LUAD (HR 1.83, p=8e-5), corroborating previous data 24 . MCT-4 was also the transporter that was identi ed to regulate glycolytic ux 15 .…”

Section: Deregulation Of Transporterssupporting

confidence: 90%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Preprint

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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…Unexpectedly, our results demonstrated that CUP patients with positive GLUT1 and CAIX expression presented significantly higher overall survival, and the same was observed for the co-expression of these proteins with MCT4 and MCT1/CD147 co-expression. Currently, most studies in the literature have shown that hyperglycolytic tumors present a poorer prognosis and decreased survival rates ( 38 , 39 , 45 , 46 ). Conversely, our results indicate a different behavior of this metabolic phenotype in CUP.…”

Section: Discussionmentioning

confidence: 99%

Expression of Glycolysis-Related Proteins in Cancer of Unknown Primary Origin

Bonatelli

¹

,

Fornari

²

,

Bernécule

³

et al. 2021

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IntroductionCancer of unknown primary origin (CUP) is defined as metastatic cancer without identification of the primary site. Considering that only 15–20% of patients with CUP show a favorable outcome, identifying biomarkers may help improve the clinical management of patients who do not respond well to conventional therapies. In this context, the study of the metabolic profile of CUP may pave the way to establish new biomarkers and/or therapeutic targets; therefore, this study aimed to characterize the expression of metabolism-related proteins in CUP.Materials and MethodsThe expression of monocarboxylate transporters MCT1, MCT2 and MCT4, their chaperone CD147, the glucose transporter GLUT1 and the pH regulator CAIX was evaluated by immunohistochemistry in a series of 118 CUP patients, and the results were associated with the available clinicopathological information.ResultsThe metabolism-related proteins MCT1, MCT4, CD147, GLUT1 and CAIX were expressed in a critical portion of the CUP (approximately 20 to 70%). MCT1 and CD147 were both more frequently expressed in cases with lymph nodes as metastasis dominant sites (p = 0.001) as well as in samples from lymph nodes (p <0.001 and p = 0.002, respectively), while MCT1 expression was more frequently expressed in squamous cell carcinomas (p = 0.045). A higher overall survival was observed in patients with tumors positive for GLUT1 and CAIX expression (p = 0.011 and p = 0.041, respectively), but none of the proteins was an independent prognostic factor for overall survival in multivariable analysis.ConclusionThe results suggest that a portion of CUPs present a hyperglycolytic phenotype, which is associated with higher overall survival.

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MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

Cited by 29 publications

References 78 publications

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Expression of Glycolysis-Related Proteins in Cancer of Unknown Primary Origin

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