Clinicopathological and prognostic involvements of MCT1, MCT4 and IL7R in esophageal squamous cell carcinoma

Abstract

BackgroundMCTs, short for monocarboxylate transporters, especially MCT1 and MCT4, have been widely touched upon in a variety of immune and cancer cells; however, they have been rarely described in esophageal squamous cell carcinoma (ESCC). IL7R, receptor of interleukin 7, has been shown to operate in several cancers; though, the clinicopathological implication of IL7R expression in ESCC remains less known. MethodsHerein, to understand the clinicopathological involvements of MCT1, MCT4 and IL7R expression in ESCC, immunohistochemistry was performed with ESCC tissue microarray comprising 86 paired ESCC and its matched normal control dots. Subsequently, statistical analyses ensued. ResultsIt was shown that concomitant expression of MCT1, MCT4 and IL7R prevailed in the stromal compartment of ESCC tissues relative to the epithelial. Moreover, up-regulated MCT1 and MCT4 were markedly associated with tumor size; while IL7R was displayed to closely correlate with lymph node metastases and clinical stage. Elevated MCT1, MCT4 and IL7R were strikingly associated with adverse outcome of ESCC. ConclusionsTogether, the data we presented here indicate that MCT1/4 and IL7R were heavily involved in the oncogenesis of ESCC.

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 ].…”

“…VECTASTAIN Elite ABC Kit, Vector Laboratories (14 articles [ 27 , 41 , 42 , 45 , 46 , 47 , 50 , 51 , 56 , 57 , 59 , 65 , 69 , 76 ]). Five studies do not refer to the IHQ kit but refer to the automated system where IHQ was performed [ 46 , 47 , 54 , 56 , 69 ], and ten studies do not refer to any detail regarding the IHQ protocol (kit or system) [ 30 , 44 , 53 , 58 , 61 , 62 , 63 , 64 , 72 , 75 ].…”

“…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.…”

“…Kim et al [ 60 ], Pinheiro et al [ 45 ] and Mikkilineni et al [ 53 ] observed that patients with high MCT1 expression tended to suffer disease recurrence [ 53 ] or progression [ 45 , 60 ]. Additionally, associations with vascular invasion [ 27 , 44 , 76 ] and the presence of proximal (lymph node) and/or distant metastasis [ 41 , 44 , 49 , 55 , 60 , 62 , 63 , 74 , 75 ] were also commonly noted. In contrast, Sukeda et al [ 47 ] reported that MCT1 expression was inversely associated with regional lymph node metastasis.…”