Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR/ALK wild-type advanced non-small cell lung cancer.

Immunotherapy has become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). At present, none of these existing biomarkers can effectively stratify true responders and there is an urgent need for identifying novel biomarkers. Exosomes derived from the serum of patients with cancer have been proven to be reliable markers for cancer diagnosis. Here, we explored the possibility of using plasma-derived exosomal microRNAs as potential biomarkers for optimal selection of patients with advanced EGFR/ALK negative NSCLC to immunotherapy. From June 2017 to February 2019, 30 patients with advanced EGFR/ALK wild-type (WT) NSCLC who received PD-1/PD-L1 inhibitors were enrolled. The efficacy evaluation was conducted after every three cycles of treatment according to RECIST 1.1. Plasma samples of these patients were collected before the administration of PD-1/PD-L1 inhibitors as baseline, and after every three cycles if the patients achieved partial response (PR) or complete response. Plasma from seven healthy individuals was also collected as normal control. Exosomes were prepared by ultracentrifugation followed by total RNA extraction, and exosome-derived miRNAs were profiled using small RNA next-generation sequencing followed by differential expression analysis. In order to identify biomarker for better response, all five patients who achieved PR and four patients with progressive disease (PD) at efficacy evaluation were included for differential expression analysis. Based on unsupervised hierarchical clustering, exosomal miRNA expression profile was significantly altered in patients with NSCLC compared with normal controls with a total of 155 differentially expressed exosomal miRNAs. Interestingly, hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified significantly upregulated in the PD groups compared with the PR group at baseline before the treatment. In addition, we identified that hsa-miR-125b-5p, a T-cell suppressor, showed a trend of increased expression in the PD group at baseline and was significantly downregulated in the post-treatment plasma exosomes compared with pre-treatment samples of the PR patients. Patients with NSCLC represent unique plasma exosomal miRNA profiles. Hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified as potential biomarkers for predicting the efficacy of immunotherapy in advanced NSCLCs. When T-cell suppressor hsa-miR-125b-5p was downregulated during the treatment, the patients may obtain increased T-cell function and respond well to immunotherapy.

Peng XX ，Yu R ，Wu X ，Wu SY ，Pi C ，Chen ZH ，Zhang XC ，Gao CY ，Shao YW ，Liu L ，Wu YL ，Zhou Q ... -  《Journal for ImmunoTherapy of Cancer》

Serum exosomal microRNAs as predictive markers for EGFR mutations in non-small-cell lung cancer.

Current therapeutic drugs show positive effects on non-small-cell lung cancer (NSCLC) patients with mutant epidermal growth factor receptor (EGFR) expression, whereas a lesser beneficial effect is generally noted on NSCLC patients with wild-type EGFR. Therefore, identification of new detection methods for the accurate clinical diagnosis of NSCLC is essential. In this study, tumor-derived exosomes from the plasma of EGFR mutation and wild-type NSCLC patients were isolated. Extensive exosomal miRNA profiling of EGFR mutation and wild-type NSCLC patients, in comparison with healthy individuals, was performed using miRNA-sequencing analysis. The variation of exosomal miRNA expression between control group (NR) and NCSLC samples (AM and AW) was identified. 96 significantly different expressed miRNAs were identified. Of these, 39 miRNAs were upregulated and 57 were downregulated. 11 miRNAs were downregulated, and 31 miRNAs were upregulated in the miRNA expression between NR and AM. Compared with healthy donors, 54 upregulated miRNAs and 36 downregulated miRNAs were observed in samples from AW patients. 40 different expressed miRNAs were identified in AM samples, compared with AW. Ten of upregulated miRNAs are miR-260, miR-1169, miR-117, miR-15b-5p, miRNA-731, miR-342-5p, miR- 898, miR-1384, miR-56, and miR-1214. Ten of downregulated miRNAs are miR-99b-5p, miR-1116, miR-689, miR-818, miR-604, miR-72, miR-955, miR-403, miR-1228, and miR-836. The exosomal miR-1169 and miR-260 as potential candidates, which contain specific characteristics that can distinguish between wild-type EGFR and mutant EGFR NSCLC patients in early-stage cancers.

Xia J ，Luo M ，Dai L ，Wang L ，Wang L ，Zhu J ... -  《-》

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer.

Shimada Y ，Matsubayashi J ，Kudo Y ，Maehara S ，Takeuchi S ，Hagiwara M ，Kakihana M ，Ohira T ，Nagao T ，Ikeda N ... -  《Scientific Reports》

Cerebrospinal fluid exosomal microRNAs as biomarkers for diagnosing or monitoring the progression of non-small cell lung cancer with leptomeningeal metastases.

Li H ，Xia M ，Zheng S ，Lin Y ，Yu T ，Xie Y ，Shen Y ，Liu X ，Qian X ，Yin Z ... -  《-》

Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer.

Chen X ，Xu Y ，Liao X ，Liao R ，Zhang L ，Niu K ，Li T ，Li D ，Chen Z ，Duan Y ，Sun J ... -  《-》