Jie He1,2,3, Hongli Huang1,2,3, Yanlei Du1,2,3, Dong Peng1,2,3, Youlian Zhou1,2,3, Yuyuan Li1,2,3, Hong Wang1,2,3, Yongjian Zhou4,5,6, Yuqiang Nie7,8,9. 1. Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. 2. Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, 510180, China. 3. Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou, 510180, China. 4. Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. yjzhou@gzhmu.edu.cn. 5. Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, 510180, China. yjzhou@gzhmu.edu.cn. 6. Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou, 510180, China. yjzhou@gzhmu.edu.cn. 7. Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. eynieyuqiang@scut.edu.cn. 8. Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, 510180, China. eynieyuqiang@scut.edu.cn. 9. Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou, 510180, China. eynieyuqiang@scut.edu.cn.
Abstract
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.
PURPOSE:DCBLD2 expression dysregulation has been reported in several types of humancancer. 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.
Authors: Shideh Mirhadi; Shirley Tam; Quan Li; Nadeem Moghal; Nhu-An Pham; Jiefei Tong; Brian J Golbourn; Jonathan R Krieger; Paul Taylor; Ming Li; Jessica Weiss; Sebastiao N Martins-Filho; Vibha Raghavan; Yasin Mamatjan; Aafaque A Khan; Michael Cabanero; Shingo Sakashita; Kugeng Huo; Sameer Agnihotri; Kota Ishizawa; Thomas K Waddell; Gelareh Zadeh; Kazuhiro Yasufuku; Geoffrey Liu; Frances A Shepherd; Michael F Moran; Ming-Sound Tsao Journal: Nat Commun Date: 2022-04-05 Impact factor: 14.919
Authors: Pan Xie; Jun-Yan Liu; Han Yan; Zhi-Bin Wang; Shi-Long Jiang; Xi Li; Zhao-Qian Liu Journal: Front Pharmacol Date: 2022-08-11 Impact factor: 5.988