IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment

Journal of Thoracic Disease

article

Liuying Huang¹  Yuan Yin¹  Danqi Qian²  Yulin Cao¹  Duo Wang¹  Xiaohan Wu¹  Liang Ming¹  Zhaohui Huang¹  Leyuan Zhou² 

[1] Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University;Department of Radiation Oncology, Affiliated Hospital of Jiangnan University;Department of Radiation Oncology, Dushu Lake Hospital Affiliated to Soochow University;State Key Laboratory of Radiation Medicine and Protection, Soochow University

关键词: Non-small cell lung cancer (NSCLC);    angiogenesis;    bevacizumab;    pulmonary hemoptysis;   

DOI  :  10.21037/jtd-23-389

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Lung cancer has some of the highest morbidity and mortality worldwide among cancers, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer diagnoses. Severe pulmonary hemorrhage (PH) is a serious potential adverse event in the treatment of lung cancer with bevacizumab. Significant clinical differences have been observed between patients with lung adenocarcinoma (LUAD) and those with lung squamous cell carcinoma (LUSC) after bevacizumab treatment; however, the underlying causes is unclear and requires further study. Methods: First, tumor tissues from LUAD and LUSC patients were stained with antibodies targeting CD31 and CD34 to assess the difference in microvessel density (MVD). Tube formation assays were performed using HMEC-1 cells cocultured with lung cancer cells. Single-cell sequencing data obtained from lung cancer tissues were then downloaded and analyzed to identify differentially expressed genes related to angiogenesis in LUAD and LUSC tumors. Real-time polymerase chain reaction, immunofluorescence analysis, small interfering RNA analysis, and enzyme-linked immunosorbent assay were performed to clarify the underlying causes. Results: The MVD of LUAD tissues was higher than that of LUSC tissues. Additionally, endothelial cells cocultured with LUAD cells had a higher MVD than did those cocultured with LUSC cells. Although bevacizumab mainly targets vascular endothelial growth factor (VEGF), the expression of VEGF 0.05). Further experiments showed that interferon regulatory factor 7 (IRF7) and interferoninduced protein with tetratricopeptide repeats 2 (IFIT2) were differentially expressed between LUSC and LUAD tumors. Higher IRF7 levels and lower IFIT2 levels in LUAD tumors were associated with higher MVD in LUAD tissues, which may be responsible for the different hemorrhage outcomes after bevacizumab treatment. Conclusions: Our data indicated that IRF7 and IFIT2 may account for the differential hemorrhage outcomes in patients with NSCLC after bevacizumab treatment, revealing a new mechanism underlying bevacizumab-induced pulmonary hemoptysis.

【 授权许可】

Unknown