Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery

Yu Akazawa,Tetsuya Nakatsura,Yasunari Nakamoto,Shoichi Mizuno,Toshihiro Suzuki,Norihiro Fujinami,Takahiro Ochiya,Yusuke Yoshioka

doi:10.1038/s41598-019-42392-7

Yu Akazawa, Tetsuya Nakatsura + Show 6 more

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https://doi.org/10.1038/s41598-019-42392-7

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Biliary tract cancer (BTC) is an aggressive type of malignant tumour. Even after radical resection, the risk of recurrence is still high, resulting in a poor prognosis. Here, we investigated the usefulness of serum miRNAs as predictive markers of recurrence and prognosis for patients with BTC after radical surgery using 66 serum samples that were collected at three time points from 22 patients with BTC who underwent radical surgery. Using microarray analysis, we successfully identified six specific miRNAs (miR-1225-3p, miR-1234-3p, miR1260b, miR-1470, miR-6834-3p, and miR-6875-5p) associated with recurrence and prognosis of BTC after radical surgery. In addition, using a combination of these miRNAs, we developed a recurrence predictive index to predict recurrence in patients with BTC after operation with high accuracy. Patients having higher index scores (≥ cut-off) had significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with lower index scores (<cut-off). Furthermore, the index was an independent factor related to RFS and OS by univariate and multivariate analyses using a Cox hazard proportional model. Overall, our results provided compelling evidence for the potential usefulness of specific serum miRNAs as effective predictive tools for recurrence and prognosis in patients with BTC who underwent radical surgery.

Highlights

Biliary tract cancer (BTC) is as one of the most aggressive types of malignant tumours and is associated with a poor prognosis
Using miRNA expression profiles of BTC tissue samples extracted from The Cancer Genome Atlas (TCGA) database, Wang et al showed that six miRNAs could serve as predictive markers for the prognosis of patients with BTC37
There were no significant differences in pre-operative CA19-9 or Carcinoembryonic antigen (CEA) values or in pathological differentiation degree and lymph metastasis between the two groups

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Introduction

Biliary tract cancer (BTC) is as one of the most aggressive types of malignant tumours and is associated with a poor prognosis. In association with BTC, circulating miRNAs in blood, including miR-2132, miR-26a33, miR-106a34, miR-19235, and combinations of several miRNAs36, have been reported as diagnostic or prognostic biomarkers These miRNAs have been shown to contribute to the proliferation, migration, invasion, and chemoresistance of tumours. Using miRNA expression profiles of BTC tissue samples extracted from The Cancer Genome Atlas (TCGA) database, Wang et al showed that six miRNAs (miR-483-5p, miR-675, miR-139-3p, miR-598, miR-625, and miR187) could serve as predictive markers for the prognosis of patients with BTC37.

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