계명대학교 의학도서관 Repository

Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients

Metadata Downloads
Author(s)
Ilseon HwangJeong Won KimKris YlayaEun Joo ChungHaruhisa KitanoCandice PerryJun HanaokaJunya FukuokaJoon‑Yong ChungStephen M. Hewitt
Keimyung Author(s)
Hwang, Il Seon
Department
Dept. of Pathology (병리학)
Journal Title
Journal of Translational Medicine
Issued Date
2020
Volume
18
Keyword
Tumor-associated macrophageCD163+/CD68+ ratioVascular endothelial growth factorAngiogenesisLymphangiogenesisNon-small cell lung cancerPrognosis
Abstract
Background:
The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC).

Methods:
Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system.

Results:
CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratiohigh and VEGF-Chigh (M2 ratiohighVEGF-Chigh) was correlated with worse overall survival (p = 0.033). Multivariate analysis revealed that M2 ratiohigh [HR (95% CI) = 1.53 (1.01–2.33), p = 0.046] and combined M2 ratiohighVEGF-Chigh expression [HR (95% CI) = 2.01 (1.28–3.16), p = 0.003] were independent predictors of poor overall survival. Notably, we confirmed that M2 macrophages significantly enhanced the protein and mRNA expression of both VEGF-A and VEGF-C, while M1 macrophages induced only mRNA expression of VEGF-A in A549 cells.

Conclusions:
This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.
Keimyung Author(s)(Kor)
황일선
Publisher
School of Medicine (의과대학)
Citation
Ilseon Hwang et al. (2020). Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients. Journal of Translational Medicine, 18, 443. doi: 10.1186/s12967-020-02618-z
Type
Article
ISSN
1479-5876
Source
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02618-z
DOI
10.1186/s12967-020-02618-z
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43465
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
공개 및 라이선스
  • 공개 구분공개
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.