Oncotarget

Research Papers:

MicroRNA-203 predicts human survival after resection of colorectal liver metastasis

T. Peter Kingham, Hoang C.B. Nguyen, Jian Zheng, Ioannis T. Konstantinidis, Eran Sadot, Jinru Shia, Deborah Kuk, Steven Zhang, Leonard Saltz, Michael I. D’Angelica, William R. Jarnagin, Hani Goodarzi and Sohail F. Tavazoie _

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Oncotarget. 2017; 8:18821-18831. https://doi.org/10.18632/oncotarget.13816

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Abstract

T. Peter Kingham2,*, Hoang C.B. Nguyen1,*, Jian Zheng2, Ioannis T. Konstantinidis2, Eran Sadot2, Jinru Shia3, Deborah Kuk4, Steven Zhang1, Leonard Saltz5, Michael I. D’Angelica2, William R. Jarnagin2, Hani Goodarzi6,7,8, Sohail F. Tavazoie1,5

1Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA

2Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

3Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

6Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA

7Department of Urology, University of California, San Francisco, San Francisco, CA, USA

8Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

*These authors contributed equally to this work

Correspondence to:

T. Peter Kingham, email: [email protected]

Hani Goodarzi, email: [email protected]

Sohail F. Tavazoie, email: [email protected]

Keywords: microRNA, miR-203, colorectal liver metastasis, survival, resection

Received: July 25, 2016     Accepted: November 14, 2016     Published: December 07, 2016

ABSTRACT

Background: Resection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.

Results: MiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).

Materials and Methods: We employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.

Conclusions: After CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation.


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