TY - JOUR
T1 - MicroRNA-203 predicts human survival after resection of colorectal liver metastasis
AU - Kingham, T. Peter
AU - Nguyen, Hoang C.B.
AU - Zheng, Jian
AU - Konstantinidis, Ioannis T.
AU - Sadot, Eran
AU - Shia, Jinru
AU - Kuk, Deborah
AU - Zhang, Steven
AU - Saltz, Leonard
AU - D'Angelica, Michael I.
AU - Jarnagin, William R.
AU - Goodarzi, Hani
AU - Tavazoie, Sohail F.
N1 - Funding Information:
We thank Connie Zhao of the Genomics Resource Center in the Rockefeller University for assistance in highthroughput sequencing. This study was supported by The Rockefeller University Center for Digestive Disease Studies, The Helmsley Foundation (ST), by NCI R00 CA194077 (HG), and by NIH/NCI Cancer Center Support Grant P30 CA008748.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Colorectal liver metastasis
KW - MiR-203
KW - MicroRNA
KW - Resection
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85015717035&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13816
DO - 10.18632/oncotarget.13816
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AN - SCOPUS:85015717035
SN - 1949-2553
VL - 8
SP - 18821
EP - 18831
JO - Oncotarget
JF - Oncotarget
IS - 12
ER -