Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab

Kazuki Sudo, Ken Kato, Juntaro Matsuzaki, Satoko Takizawa, Yoshiaki Aoki, Hirokazu Shoji, Satoru Iwasa, Yoshitaka Honma, Atsuo Takashima, Hiromi Sakamoto, Tomoaki Naka, Shigeki Sekine, Narikazu Boku, Takahiro Ochiya

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Background: Nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, showed promising activity for the treatment of advanced esophageal squamous-cell carcinoma in a phase II study (ONO-4538-07; JapicCTI-No.142422). We explored serum microRNA (miRNA) candidate predictive markers of the response to nivolumab. Methods: In the phase II study, 19 patients received nivolumab (3 mg/kg IV Q2W) at National Cancer Center Hospital. The expression of 2565 serum miRNAs before and during treatment was analyzed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.). Immune-related response evaluation criteria used to evaluate response and miRNA expression were compared between responders and non-responders. The top 20 miRNAs by accuracy in receiver operating characteristic curve analysis were identified by leave-one-out cross-validation, and those with the area under curve values > 0.8, cross-validated accuracy > 0.8, and a 0.5 difference in the average log2 expression level between responders and non-responders were further analyzed. Results: Of the 19 patients, five responded to nivolumab. We identified miRNAs related to the response to nivolumab, including one detected in the serum before treatment (miR-1233-5p; AUC = 0.895) and three present after treatment (miR-6885-5p, miR-4698 and miR-128-2-5p; AUC = 0.93, 0.97 and 0.93, respectively). Conclusions: Candidate miRNAs capable of predicting the response to nivolumab were identified in the serum of patients with advanced esophageal squamous-cell carcinoma in ONO-4538-07.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalJapanese journal of clinical oncology
Volume50
Issue number2
DOIs
Publication statusPublished - 2019 Dec 23
Externally publishedYes

Keywords

  • GI-esophagus-med
  • chemo-GI tract
  • immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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