Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab.
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.
['Sudo|Kazuki|K|', 'Kato|Ken|K|', 'Matsuzaki|Juntaro|J|', 'Takizawa|Satoko|S|', 'Aoki|Yoshiaki|Y|', 'Shoji|Hirokazu|H|', 'Iwasa|Satoru|S|', 'Honma|Yoshitaka|Y|', 'Takashima|Atsuo|A|', 'Sakamoto|Hiromi|H|', 'Naka|Tomoaki|T|', 'Sekine|Shigeki|S|', 'Boku|Narikazu|N|', 'Ochiya|Takahiro|T|']
D000368:Aged D000074322:Antineoplastic Agents, Immunological D019540:Area Under Curve D004938:Esophageal Neoplasms D000077277:Esophageal Squamous Cell Carcinoma D005260:Female D020869:Gene Expression Profiling D006801:Humans D008297:Male D035683:MicroRNAs D008875:Middle Aged D000077594:Nivolumab D061026:Programmed Cell Death 1 Receptor D012372:ROC Curve
GI-esophagus-med chemo-GI tract immunotherapy