Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer
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Chang Liu1,4, Cathy Eng1, Jianjun Shen3, Yue Lu3, Yoko Takata3, Amir Mehdizadeh1, George J. Chang2, Miguel A. Rodriguez-Bigas2, Yanan Li1, Ping Chang1, Yixiang Mao1, Manal M. Hassan1, Fangyu Wang4, Donghui Li1
1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA
4Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Nanjing, China
Donghui Li, email: [email protected]
Fangyu Wang, email: [email protected]
Keywords: exosome, microRNA, colon cancer, qRT-PCR, Illumina RNA sequencing
Received: April 22, 2016 Accepted: October 11, 2016 Published: October 24, 2016
Purpose: The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer.
Results:145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0.002). The reduced expression was significantly related to increased risk of tumor recurrence and risk of death. As a predictor for tumor recurrence, ROC analysis revealed the AUC (95% CI) was 0.72 (0.59-0.85, P=0.001) for lower level of miR-4772-3p compared to 0.63 (0.51-0.75, P=0.062) for tumor site and 0.65 (0.51-0.78,P=0.034) for lymph node status. Among 66/84 patients who received FOLFOX adjuvant therapy, 9/10 (90%) patients with a lower level and 10/56 (18%) patients with a higher level of miR-4772-3p had tumor recurrence (P<0.001).
Materials and Methods: Blood samples were prospectively collected from84 patients with stage II/III colon cancer after tumor resection and before adjuvant therapy. Serum exosomal miRNA profiles were determined by RNA sequencing. Differentially expressed mature miRNAs were identified between patients with or without tumor recurrence. The top hits were validated in individual RNA samples using quantitative real-time reverse transcription PCR.
Conclusions: Reduced expression of serum exosomal miR-4772-3p is a prognostic biomarker for tumor recurrence in stage II and stage III colon cancer patients. The predictive value of this marker for response to FOLFOX adjuvant therapy needs further investigation.
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