BDNF is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and is associated with brain metastasis

作者全名："Yu, Qian; Wang, Yitian; Yi, Guangming; Yang, Wendi; Chen, Kehong; Tan, Xiangwu; Zhang, Xiaoyue; Xu, Zaicheng; Yang, Zhenzhou; Peng, Yuan"

作者地址："[Yu, Qian; Wang, Yitian; Yi, Guangming; Yang, Wendi; Chen, Kehong; Tan, Xiangwu; Zhang, Xiaoyue; Xu, Zaicheng; Yang, Zhenzhou; Peng, Yuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing 400010, Peoples R China"

通信作者："Yang, ZZ; Peng, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing 400010, Peoples R China."

来源：IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000867895200001

JCR分区：Q2

影响因子：6.4

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：biomaker(5); brain metastasis(4); brain-derived neurotrophic factor(1); lung adenocarcinoma(2); tumour immune microenvironment(3)

摘要："Non-small cell lung cancer (NSCLC) is one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies, particularly lung adenocarcinoma (LUAD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has been linked to several human malignancies and has been shown to promote LUAD tumorigenesis. However, its function in the tumour immune microenvironment (TIME) remains largely unexplored, especially in complex brain tissue environments. In this study, BDNF was found to be particularly increased in patients with advanced tumour stage, lymphatic metastasis, and distant metastasis, indicating a correlation with LUAD progression. We characterized the prognostic value of BDNF and defined BDNF as an unfavourable prognostic indicator through a common driver gene-independent mechanism in LUAD. Furthermore, patients with increased BDNF levels in primary LUAD might have a higher risk of developing brain metastasis (BM), and central nervous system (CNS) metastasis showed an elevated expression of BDNF compared to their matched primary lesions. Additionally, we investigated the interaction between BDNF and infiltrating immune cells in both primary lesions and paired BM using multiplex immunostaining. The results showed that BDNF might drive an immunosuppressive tumour microenvironment (TME) by re-education of tumour-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype, particularly in BM. Our findings demonstrate that BDNF serves as an independent potential prognostic marker and correlates with BM in LUAD. As it is closely related to TAM polarization, BDNF may be a promising immune-related biomarker and molecular target in patients with LUAD."

基金机构：China Postdoctoral Science Foundation [2022T150777]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [KRYCYQ-2116]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0208]

基金资助正文："China Postdoctoral Science Foundation, Grant/Award Number: 2022T150777; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University, Grant/Award Number: KRYCYQ-2116; the Natural Science Foundation of Chongqing, Grant/Award Number: cstc2020jcyj-msxmX0208"