Monocarboxylate Transporters 1 and 4 and MTCO1 in Gastric Cancer

Abstract

Background: Monocarboxylate transporters (MCTs) appear to play an important role in tumor development and aggressiveness. The present study aimed to evaluate associations between cytoplasmic MCT1, MCT4, and mitochondrial cytochrome c oxidase (MTCO1) expression and clinicopathological variables or survival in gastric cancer. Material and methods: A total of 568 gastric adenocarcinoma patients were included in this retrospective cohort study. Protein expressions were detected by immunohistochemical staining. The patients were divided into low expression and high expression groups by median value. The Chi-squared test was used to compare categorical variables. The T-test was used to compare continuous variables. Expressions were analyzed in relation to 5-year survival and overall survival. Cox regression provided HRs and 95% CIs, adjusted for confounders. Results: High cytoplasmic MCT1 expression was associated statistically significantly with higher T-class (p = 0.020). High cytoplasmic MCT4 expression was associated statistically significantly with positive lymph node status (p = 0.005) and was more common in Lauren’s intestinal type (p < 0.001). Low cytoplasmic MTCO1 expression was associated statistically significantly with positive distant metastases (p = 0.030), and high cytoplasmic MTCO1 expression was associated more often with intestinal type (p = 0.044). However, MCT1, MCT4, and MTCO1 were not associated with survival. Conclusions: Monocarboxylate receptors seem to be associated with gastric cancer progression but have no independent prognostic relevance.

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

“…Patient ages ranged between 18 to 98 years, and all samples were collected from adult patients (considering the studies where information on age was available). MCT1 expression was assessed in different cancers: one study in melanoma [ 41 ], oral cavity tumours [ 42 ], endometrial cancer [ 43 ], testicular germ cell tumours [ 44 ], soft tissue sarcoma [ 45 ], head and neck cancer [ 46 ], pancreatic ductal adenocarcinoma (PDAC) [ 47 ], small bowel neuroendocrine tumours [ 48 ], synovial sarcoma [ 49 ], adrenocortical carcinoma [ 50 ], small cell lung cancer (SCLC) [ 35 ], gastrointestinal stromal tumours (GIST) [ 51 ], osteosarcoma [ 30 ], malignant pleural mesothelioma [ 52 ], Hodgkin lymphoma [ 53 ], oropharyngeal squamous cell carcinoma (OSCC) [ 54 ] and cancer of unknown primary origin [ 55 ]; two studies in prostate adenocarcinoma [ 56 , 57 ], colorectal cancer (CRC) [ 58 , 59 ], clear cell renal cell carcinoma (RCC) [ 60 , 61 ], esophageal squamous cell carcinoma (ESCC) [ 62 , 63 ], non-Hodgkin lymphoma (NHL) [ 64 , 65 ] and gastric cancer [ 66 , 67 ]; three studies in non-small cell lung cancer (NSCLC) [ 68 , 69 , 70 ] and breast cancer [ 71 , 72 , 73 ]; and four studies in bladder cancer [ 27 , 74 , 75 , 76 ].…”

“…Concerning the evaluation of MCT1 expression through immunohistochemistry (IHQ) (summarised in Table 2 ), the most commonly used primary antibody was AB3538P, rabbit polyclonal, from Chemicon International (16 out of the 39 included studies [ 27 , 41 , 42 , 44 , 45 , 50 , 51 , 52 , 55 , 56 , 59 , 60 , 65 , 69 , 74 , 76 ]). Nine publications did not report the antibody reference [ 30 , 53 , 54 , 61 , 66 , 67 , 71 , 72 , 75 ], and two publications used an in-house antibody [ 35 , 58 ]. The most commonly used IHQ kit was R.T.U.…”

“…Most studies did not mention positive or negative controls [ 30 , 35 , 47 , 49 , 51 , 52 , 53 , 55 , 56 , 58 , 60 , 61 , 62 , 64 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Two and six studies (respectively) reported the use of negative [ 43 , 46 ] or positive [ 42 , 44 , 48 , 54 , 60 , 66 ] controls, and eight studies reported using both negative and positive controls [ 27 , 41 , 45 , 50 , 57 , 59 , 63 , 65 ]. For negative controls, replacement or abolishment of primary antibodies were the most reported methods; for positive controls, the most used samples were colon and colorectal carcinoma.…”

“…Frequent associations were found between elevated MCT1 protein levels and larger tumours [ 60 , 63 , 71 , 72 ], as well as higher disease stage and/or grade [ 27 , 41 , 44 , 45 , 50 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 71 , 73 , 74 ]. Of note, Afonso et al, 2016 [ 76 ] reported the same associations when MCT1 was expressed by normoxic cancer cells.…”

“…MCT1 nuclear expression was found to be associated with higher overall survival of soft-tissue sarcoma patients in the study by Pinheiro et al [ 45 ]. On the other hand, ten studies reported that MCT1 expression did not have an impact on prognostic parameters [ 44 , 48 , 52 , 54 , 57 , 58 , 65 , 66 , 68 , 70 ].…”