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

Abstract

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.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status

“…Although the role of BDNF in the TIME of cervical cancer has not been investigated yet, this evidence may suggest the role of BDNF in modulating the immune response also in patients with cervical cancer. In this context, the immune system depletion associated with HIV infection may exert a role in enhancing the immunosuppressive TIME driven by BDNF [ 32 ]. HIV predominantly infects and replicates within CD4+ T cells, which play a central role in orchestrating the immune response.…”

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

“…The increased expression of activated leukocyte cell adhesion molecule (ALCAM) is significantly correlated with upregulation in NSCLC brain metastases, leading to reduced survival times [83]. Brain-derived neurotrophic factor (BDNF) levels in primary LUAD have been linked to a heightened risk of brain metastasis development, with brain metastases expressing higher BDNF levels than their primary lesion counterparts [84]. Furthermore, other tissue markers, including cholecystokinin A receptor (CCKAR) and WD repeat domain 5 (WDR5), are significantly associated with brain metastasis and have emerged as independent risk factors [85,86].…”