Abstract
The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) have been shown to be involved in tumorigenesis of various cancers. However, their roles in colorectal cancer (CRC) remain unclear. In this study, we explored the expressions of MAL2 and TPD52 in tumor specimens resected from 123 CRC patients and the prognostic values of the two proteins in CRC. Immunohistochemical analyses showed that MAL2 (P<0.001) and TPD52 (P<0.001) were significantly highly expressed in primary carcinoma tissues compared with adjacent non-cancerous mucosa tissues. And TPD52 exhibited frequent overexpression in liver metastasis tissues relative to primary carcinoma tissues (P = 0.042), while MAL2 in lymphnode and liver metastasis tissues showed no significant elevation. Real-time quantitative PCR (RT-qPCR) showed the identical results. Correlation analyses by Pearson’s chi-square test demonstrated that MAL2 in tumors was positively correlated with tumor status (pathological assessment of regional lymph nodes (pN, P = 0.024)), and clinic stage (P = 0.017). Additionally, the expression of TPD52 was detected under the same condition and was shown to be positively correlated withtumor status (pathological assessment of the primary tumor (pT, P = 0.035), distant metastasis (pM, P = 0.001)) and CRC clinicopathology(P = 0.024). Kaplan-Meier survival curves indicated that positive MAL2 (P<0.001) and TPD52 (P<0.001) expressions were associated with poor overall survival (OS) in CRC patients. Multivariate analysis showed that MAL2 and TPD52 expression was an independent prognostic factor for reduced OS of CRC patients. Moreover, overexpression of TPD52 in CRC SW480 cells showed an increased cell migration (P = 0.023) and invasion (P = 0.012) through inducing occurrence of epithelial-mesenchymal transition (EMT) and activating focal adhesion kinase (FAK)-mediated integrin signalling and PI3K⁄Akt signalling.Whereas TPD52-depleted cells showed the reverse effect. These data suggested that MAL2 and TPD52 might be potential biomarkers for clinical prognosis and might be a promising therapeutic target for CRC.
Highlights
Colorectal cancer (CRC) is known as a widespread malignant tumor, representing the third most common cancer in both men and women [1]
To validate whether MAL2 and TPD2 are involved in colorectal cancer (CRC) carcinogenesis, we examined expression of the two proteins in the paired tumors, lymph nodes, liver metastasis and adjacent non-cancerous mucosa tissues from CRC patients (n = 123) by immunohistochemical staining.As shown in Table 1, both MAL2 (n = 123, P
These results suggested that MAL2 and tumor protein D52 (TPD52) were involved in tumorigenesis and TPD52 might be associated with liver metastasis of CRC
Summary
Colorectal cancer (CRC) is known as a widespread malignant tumor, representing the third most common cancer in both men and women [1]. The four-transmembrane protein MAL2 whose gene is located on chromosome 8q, commonly identified to be correlated with membrane apposition events[7], was found to be overexpressed or increased in copy number in some human cancers [8,9,10,11,12,13,14,15,16,17]. MAL2 expression has been shown to be elevated by independent expression microarray studies in ovarian cancer [18,19,20] and increased at RNA and protein levels in renal cell [17,21] and breast cancers[11]. The expression of MAL2 in colorectal cancer has not been still investigated, and its potential clinical significance remains unclear
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