Cancer science
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Next-generation sequencing (NGS) and digital PCR technologies allow analysis of the mutational profile of circulating cell-free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non-small cell lung cancer at earlier stages. A total of 150 matched tumor and serum samples were collected from non-small cell lung cancer patients at stages IA-IIIA. ⋯ Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA-IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation-positive patients than in the negative patients at stages T2b-T4 (159.1 ± 58.0 vs. 52.5 ± 9.9 cm3 , P = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte.
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To assess the association of the programmed cell death ligand 1 (PD-L1) with cisplatin-based neo-adjuvant chemotherapy (NAC) response, we investigated the level of PD-L1 and found increased PD-L1 expression in chemo-resistant tumors compared with chemo-sensitive tumors according to RNA-Seq analysis. In a cohort of 92 patients with NAC, the positive staining of PD-L1 was correlated with TNM stage, lower sensitive-response rates and shorter overall survival rates. In another 30 paired tumor specimens pre- and post-chemotherapy, the patients with high PD-L1 expression post-chemotherapy had a worse outcome and higher stable disease rate. ⋯ When phosphatidylinositol 3-kinase/protein kinase B signaling was inhibited by corresponding inhibitors, PD-L1 expression was downregulated and apoptosis was upregulated in the cisplatin-treated cancer cells. These results suggest that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer.