Targeting regulation of VEGF by BPTF in Non-Small Cell Lung Cancer and its potential clinical significance

Abstract Purpose VEGF facilitates the formation of tumor angiogenesis, and bevacizumab targeting VEGF is used in anti-tumor therapy. It’s meaningful to clarify the upstream regulatory mechanism of VEGF. BPTF is important in chromosomal remodeling, and promotes the progression of tumors. However, its promotion of tumor angiogenesis by targeting VEGF has not been reported. This study aims to elucidate the regulation of VEGF by BPTF and its clinical significance in NSCLC. Methods 1. Reduced the expression of BPTF by transfecting BPTF siRNA and shRNA plasmid in vivo and vitro. Examined the expressions of BPTF, VEGF and CD144 by immunofluorescence and Western Blot. 2. The expressions of BPTF, VEGF, CD144 and CD31 were detected in lung adenocarcinoma samples by immunofluorescence, Western Blot and immunohistochemical. 3. 26 lung adenocarcinoma patients treated by bevacizumab were divided into 2 groups according to the bevacizumab efficacy. BPTF and VEGF expressions were analyzed. Results 1. BPTF knockdown can inhibit the expression of VEGF and CD144 in vivo and vitro. 2. Compared with para-cancer tissues, BPTF, VEGF, CD144 and CD31 were highly expressed in lung adenocarcinoma. 3. In 75 lung adenocarcinoma specimens, BPTF and VEGF overexpression was correlated with lymph node metastasis and clinical stage. The five-year survival rate in group of BPTF and VEGF low expression was higher, and BPTF was positively correlated with VEGF. 4. Among 26 patients treated with bevacizumab, the patients with BPTF overexpresstion are more in the sensitive group. Conclusions BPTF positively regulates VEGF expression and BPTF predicts a better efficacy of bevacizumab in NSCLC.