1高雄醫學大學 泌尿學科；2高雄醫學大學附設中和紀念醫院 泌尿科；3衛生福利部屏東醫院
泌尿科；4國立中山大學 生物醫學研究所； 5高雄市立大同醫院 泌尿科；
Overexpression of Hepatoma-derived growth factor (HDGF) Is Associated with Worse Prognosis in Upper Urinary Tract Urothelial Carcinoma
Bi-Wen Yeh1,2, Wei-Ming Li1,2,3*, Ming-Hong Tai4, Ching-Chia Li1,2,5, Chun-Nung Huang1,2,
1Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan；2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 6Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Purpose: Hepatoma-derived growth factor (HDGF) is a nucleus targeted growth factor, it has been reported to exert mitogenic effects on several types of cells and elevated in various types of cancers suggesting an important role in the development and progression of cancers. Our study was designed to elucidate the correlation of HDGF expression and prognosis in patients with upper urinary tract urothelial carcinoma (UTUC). The related mechanisms of HDGF involved were investigated using urothelial cancer cell lines.
Patients and Methods: One hundred and fifty-eight UTUC specimens were analyzed for HDGF by immunohistochemistry. HDGF expression in urothelial cancer cell lines was analyzed by RT-PCR and western blotting. In vitro characterizations of the cellular function of recombinant HDGF in epithelial-mesenchymal transition (EMT) and tumorigenic behaviors were performed by trans-well assay and colony formation assay, respectively.
Results and conclusion:
Overexpression of HDGF was present in 74 patients (46.8%). A positive HDGF expression was significantly associated with higher disease progression (p=0.036) and cancer-related death rates (p= 0.001). In vitro study showed that overexpression of HDGF in non-invasive UC cells could significantly increase their cellular proliferation, colonies formation, and migration/invasion ability through the PI3K/AKT pathway. In contrast, knockdown of HDGF high expression UC cells with its specific shRNA inhibited the growth ability using colonies formation experiments. These results indicated that HDGF overexpression is associated with aggressive biological behavior of UC cells via the PI3K/AKT pathway. In conclusion, our study shown that HDGF is participated in UC disease progression processes. HDGF can be a potential prognostic prediction biomarker for patients with invasive UTUC post-operatively. Further identification of the molecular mechanisms involved and searching for specific targets related are warranted.