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Genome-wide expression profiling of mediastinal lymph nodal metastasis of stage IIIA NSCLC patients before neoadjuvant chemotherapy

ABSTRACT: Non–small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide due to late diagnosis and lack of effective therapies to treat metastatic disease. About one third of NSCLC patients present at diagnosis with locally advanced cancer (stage IIIA) which metastasizes ipsilateral mediastinal or subcarinal lymph nodes (N2). Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for resectable N2 disease. However, the majority of patients do not respond to NACT and show persistent lymph nodal metastases and an adverse outcome. Our scant knowledge of the molecular biology of lymph node metastases (LNmets) represents a major obstacle to develop more effective therapies. Here, we investigated gene expression profile (coding and non-coding) of LNmets collected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy, in two cohorts of stage IIIA patients before NACT (N=70). We discovered a microRNA expression signature in LNmets predictive of NACT response of N2 patients. Importantly, we unveiled a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance and impact T cell viability in NSCLC. Our data suggests the relevance of LNmets molecular profiling to predict response to NACT likewise presents strong evidences of a miRNA-based mechanism which functionally links chemotherapy response with PD-L1 regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193707 | GEO | 2022/12/31

REPOSITORIES: GEO

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