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

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...

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Autores principales: Huang, Liuying, Yin, Yuan, Qian, Danqi, Cao, Yulin, Wang, Duo, Wu, Xiaohan, Ming, Liang, Huang, Zhaohui, Zhou, Leyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183489/
https://www.ncbi.nlm.nih.gov/pubmed/37197507
http://dx.doi.org/10.21037/jtd-23-389
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author Huang, Liuying
Yin, Yuan
Qian, Danqi
Cao, Yulin
Wang, Duo
Wu, Xiaohan
Ming, Liang
Huang, Zhaohui
Zhou, Leyuan
author_facet Huang, Liuying
Yin, Yuan
Qian, Danqi
Cao, Yulin
Wang, Duo
Wu, Xiaohan
Ming, Liang
Huang, Zhaohui
Zhou, Leyuan
author_sort Huang, Liuying
collection PubMed
description 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 in LUSC and LUAD cells was not significantly different (P>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.
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spelling pubmed-101834892023-05-16 IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment Huang, Liuying Yin, Yuan Qian, Danqi Cao, Yulin Wang, Duo Wu, Xiaohan Ming, Liang Huang, Zhaohui Zhou, Leyuan J Thorac Dis Original Article 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 in LUSC and LUAD cells was not significantly different (P>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. AME Publishing Company 2023-04-26 2023-04-28 /pmc/articles/PMC10183489/ /pubmed/37197507 http://dx.doi.org/10.21037/jtd-23-389 Text en 2023 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Huang, Liuying
Yin, Yuan
Qian, Danqi
Cao, Yulin
Wang, Duo
Wu, Xiaohan
Ming, Liang
Huang, Zhaohui
Zhou, Leyuan
IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title_full IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title_fullStr IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title_full_unstemmed IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title_short IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
title_sort irf7 and ifit2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183489/
https://www.ncbi.nlm.nih.gov/pubmed/37197507
http://dx.doi.org/10.21037/jtd-23-389
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