Thoracic Cancer (Oct 2020)

MicroRNA‐200b is a potential biomarker of the expression of PD‐L1 in patients with lung cancer

  • Seigo Katakura,
  • Nobuaki Kobayashi,
  • Hisashi Hashimoto,
  • Chisato Kamimaki,
  • Katsushi Tanaka,
  • Sousuke Kubo,
  • Kentaro Nakashima,
  • Shuhei Teranishi,
  • Saki Manabe,
  • Keisuke Watanabe,
  • Nobuyuki Horita,
  • Yu Hara,
  • Masaki Yamamoto,
  • Makoto Kudo,
  • Hongmei Piao,
  • Takeshi Kaneko

DOI
https://doi.org/10.1111/1759-7714.13653
Journal volume & issue
Vol. 11, no. 10
pp. 2975 – 2982

Abstract

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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.

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