Suppression of MAL gene expression is associated with colorectal cancer metastasis

Abstract

Abstract. Mal, T-cell differentiation protein (MAL) is a candidate tumor suppressor gene that functions in membrane trafficking processes in polarized epithelial cells. The aim of the present study was to determine its clinical significance in colorectal cancer (CRC). The RNA and protein expression levels of MAL in 30 colorectal specimens were detected by semi-quantitative polymerase chain reaction and immunohistochemistry analysis. Statistical analysis was performed using SPSS software. The RNA level of MAL was significantly downregulated in the CRC tissues compared with the adjacent healthy tissue (P<0.05). MAL was only positively expressed in 20% of the CRC tissues, but in 66.7% of the adjacent tissues, as determined by immunohistochemistry analysis. The expression of the MAL RNA transcript exhibited a positive correlation with protein expression. The expression levels of MAL were significantly associated with different tumor-node-metastasis stages and lymph node metastasis (P<0.05), but not with age, gender, tumor site, differentiation status and pathological type (P>0.05). Suppression of MAL expression was significantly correlated with metastasis in CRC. The present study indicated that MAL may function as an anti-metastasis factor and represent a potential biomarker for malignant colorectal tumors. IntroductionColorectal cancer (CRC) is the third most common malignant cancer and the second leading cause of mortality worldwide (1). In China, the incidence rate of CRC is increasing rapidly, particular in urban areas, such as Shanghai, which was formerly considered a low-risk area (2,3). Metastasis is the main cause of mortality in CRC patients (4). The first sites of metastatic CRC are the regional lymph nodes and the liver. Investigations into the molecular mechanisms involved in CRC metastasis are of major importance in order to develop novel strategies for targeted therapies (5).The mal, T-cell differentiation protein (MAL) gene encodes the T-lymphocyte maturation-associated protein and functions in T-cell differentiation (6). Recently, downregulation of MAL has been associated with a variety of human epithelial malignancies. For example, Mimori et al (7) initially found that MAL was highly expressed in normal esophageal epithelia, but silenced in esophageal tumors. Later, inactivation of MAL was shown to be a common event in breast, head and neck, and gastric cancer (8-11). However, the functional role and mechanistic action of MAL in CRC remains largely unknown. The present study aimed to determine the clinical significance of MAL in colorectal cancer by measuring its expression level in CRC tissues. Materials and methodsTissue samples and cell line. The present study enrolled a total of 30 CRC patients who underwent surgery between 2010 and 2011 at Shanghai First People's Hospital (Shanghai, China). The patients did not receive any pre-operative cancer treatment prior to resection. Of the 30 patients, 18 were male and 22 were female, and the age of the patients ranged between 45 and 87 years (median, 6...

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

“…The results reported in Table S7 showed that high HIF-1a expression is negatively correlated with most of the markers of T cells, CD8 T cells, cytotoxic lymphocytes, NK cells, myeloid dendritic cells cell types (Pearson r < 0 and p value < 0.05, Table S7 ), and positively correlated with most of the makers of monocytic lineage, neutrophils, endothelial cells and fibroblasts (Pearson r > 0 and p value < 0.05, Table S7 ). Within the set of significantly correlated immune markers in Table S7 , we found that MAL, BANK1, CXCR2, and KCNJ15 genes have been previously reported to play a tumor suppressive role in different types of cancer [ 93 , 94 , 95 , 96 ]. These findings support the results shown in Figure 6 .…”

“…Because the tumor suppressing/promoting role of several immune markers remains controversial to date, we also assessed the potential suppressive role of the immune markers significantly correlated with HIF-1a. Bibliographic search evidenced that MAL, BANK1, CXCR2, and KCNJ15 genes play a tumor suppressive role in different types of cancer, including colorectal cancer, B-cell lymphoma, and renal cell carcinoma [ 93 , 94 , 95 , 96 ]. However, we did not find any study reporting the tumor suppressive role of these genes in NB.…”

MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis

“…The function of MAL in tumor cells is still controversial. In particular, a tumor suppressor activity was demonstrated in esophageal tumors [ 33 ], as well as in colorectal and gastric cancer [ 34 , 35 ], while an intense MAL protein expression was detected in specific types of renal carcinoma and in thyroid follicular cell-derived carcinoma [ 36 ]. Moreover, MAL was found frequently hypermethylated in colon and breast cancer, thus explaining its reduced gene expression [ 37 , 38 ].…”

Genome-wide analysis identifies colonic genes differentially associated with serum leptin and insulin concentrations in C57BL/6J mice fed a high-fat diet

“…Mal (myelin and lymphocyte protein, T-cell differentiation protein) is a tumor-suppressor gene and a diagnostic biomarker for colorectal cancer due to its inactivation by promoter hypermethylation [ 21 ]. A recent study reported that Mal downregulation is associated with colorectal cancer metastasis [ 22 ]. Hypermethylation of the Mal promoter is also found in gastric cancers, suggesting that detection of Mal methylation could be a good prognostic marker for other types of cancer [ 23 ].…”