Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance

Purpose: VEGF facilitates tumor angiogenesis, and bevacizumab targeting VEGF is used in anti-tumor therapy. It is meaningful to clarify the upstream regulatory mechanism of VEGF. BPTF is important in chromosomal remodeling, and promotes the progression of tumors. However, its role in promoting tumor angiogenesis by targeting VEGF has not been fully reported. This study aims to elucidate the expression regulation of VEGF by BPTF and its clinical significance in NSCLC. Methods: 1. BPTF siRNA and shRNA plasmids were used to reduce the expression of BPTF by transfection in vivo and in vitro. BPTF, VEGF and CD144 expressions were examined 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 staining. 3. 26 lung adenocarcinoma patients treated by bevacizumab were divided into 2 groups according to the treatment efficacy. BPTF and VEGF expressions were analyzed. Results: 1. BPTF knockdown inhibited the expression of VEGF and CD144 in vivo and in 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 5-year survival rate of patients with BPTF and VEGF low expression was higher, and BPTF expression was positively correlated with VEGF expression. 4. Among 26 patients treated with bevacizumab, the patients with BPTF overexpression are more sensitive to the treatment. Conclusions: BPTF positively regulates VEGF expression and its high expression predicts a better efficacy of bevacizumab treatment in NSCLC.

Automated summary

This study reveals that BPTF promotes tumor angiogenesis in lung adenocarcinoma by positively regulating the expression of VEGF. Higher expression of BPTF and VEGF is associated with lymph node metastasis and clinical stage, while lower expression is correlated with a higher 5-year survival rate. Furthermore, patients with BPTF overexpression are more likely to have a better response to bevacizumab treatment.