Abstract:
BACKGROUND:Advanced non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. However, outcomes have gradually improved after the introduction of novel immunotherapies, including immune checkpoint inhibitors (ICIs). Although programmed death-ligand 1 (PD-L1) expression in tumor tissues is a known biomarker for guiding ICI treatment of NSCLC, challenges such as difficulty of liquid biopsy and heterogeneous results during treatment persist. This study evaluated the potential of miR200b as a surrogate biomarker for PD-L1 expression. METHODS:We used the human lung cancer cell lines H226, H460, H520, A549, and H1975. miR200b expression in blood and bronchoscopy specimens of NSCLC patients was evaluated using reverse-transcription-quantitative PCR. Using flow cytometry, PD-L1 expression in vitro, as well as in tumor tissues, was evaluated after transfection with a mimic miR200b or siRNA. RESULTS:miR200b expression negatively correlated with PD-L1 expression in all cell lines. The induction or knockdown of miR200b also altered PD-L1 expression in vitro. The patient group with a PD-L1 tumor proportion score ≥ 50% had significantly lower miR200b expression in the bronchoscopy specimens (P = 0.025) and serum-derived exosomes (P = 0.022) than that with PD-L1 tumor proportion score < 50%. CONCLUSIONS:miR200b can regulate PD-L1 expression in lung cancer cells, and miR200b expression in clinical specimens negatively correlated with PD-L1 expression. Thus, miR200b may be a useful surrogate biomarker for PD-L1 expression in lung cancer patients. KEY POINTS:SIGNIFICANT FINDINGS OF THE STUDY: High PD-L1 expression was linked to low miR200b expression, whereas low PD-L1 expression was linked to high miR200b expression in human lung cancer patients. Thus, miR200b overexpression or silencing can control PD-L1 expression in cancer cells. What this study adds We demonstrated the potential of miR200b as a surrogate biomarker for PD-L1 expression in lung cancer patients.
journal_name
Thorac Cancerjournal_title
Thoracic cancerauthors
Katakura S,Kobayashi N,Hashimoto H,Kamimaki C,Tanaka K,Kubo S,Nakashima K,Teranishi S,Manabe S,Watanabe K,Horita N,Hara Y,Yamamoto M,Kudo M,Piao H,Kaneko Tdoi
10.1111/1759-7714.13653subject
Has Abstractpub_date
2020-10-01 00:00:00pages
2975-2982issue
10eissn
1759-7706issn
1759-7714journal_volume
11pub_type
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