Association of DCBLD2 upregulation with tumor progression and poor survival in colorectal cancer.

PURPOSE

DCBLD2 expression dysregulation has been reported in several types of human cancer. As yet, however, the role of DCBLD2 in colorectal cancer (CRC) is not known.

METHODS

CRC tissues were obtained from patients undergoing surgery from February 2009 to May 2014 (n = 90). Tissue microarray construction and immunohistochemistry were carried out to determine DCBLD2 expression. In vivo studies were performed in 4-week-old BALB/c nude mice. In vitro studies were conducted using CRC-derived HT29 and HCT116 cell lines.

RESULTS

DCBLD2 expression was found to be significantly increased in CRC tissues compared to adjacent normal tissues (p < 0.001). In addition, we found that DCBLD2 expression was positively correlated with the stage of the disease, the degree of differentiation and vascular invasion. High DCBLD2 expression was significantly associated with a poor overall survival. In vitro, DCBLD2 expression downregulation significantly reduced CRC cell proliferation and invasion. In a mouse xenograft model, DCBLD2 expression downregulation reduced lung metastasis and increased overall survival. Gene set enrichment analysis (GSEA) revealed that DCBLD2 overexpression induces epithelial-mesenchymal transition (EMT) and activates the JAK/STAT3 pathway.

CONCLUSIONS

We found that high DCBLD2 expression correlated with a poor clinical outcome, as well as tumorigenesis, invasion and metastasis of CRC cells. DCBLD2 may serve as a prognostic biomarker and a novel therapeutic target for CRC.