The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis

PLoS One. 2017 May 31;12(5):e0178515. doi: 10.1371/journal.pone.0178515. eCollection 2017.

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.

MeSH terms

  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Humans
  • Myelin and Lymphocyte-Associated Proteolipid Proteins / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Real-Time Polymerase Chain Reaction

Substances

  • MAL2 protein, human
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Neoplasm Proteins
  • TPD52 protein, human

Grants and funding

This project was supported by the National Natural Science Foundation of China (NSFC, Grant No. 1272704 and 81402367), the Science & Technology Bureau of Harbin (No. 2014RFQGJ and 2015RAXYJ063) and Research Fund for the Doctoral Program of Higher Education (SRFDP, No. 20132307120012), Heilongjiang postdoctoral fund (No. LBH-Z12155) and Harbin Municipal Science and Technology Committee of Harbin outstanding academic leaders plan (No. 2015RAXYJ063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.