title: Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer.
abstract: OBJECTIVE
  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).
  
  
  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.
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Nanjing, China.
authors: Chang
authors: C
authors: Liu
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Cathy
authors: C
authors: Eng
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA.
authors: Jianjun
authors: J
authors: Shen
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA.
authors: Yue
authors: Y
authors: Lu
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA.
authors: Yoko
authors: Y
authors: Takata
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Amir
authors: A
authors: Mehdizadeh
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: George J
authors: GJ
authors: Chang
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Miguel A
authors: MA
authors: Rodriguez-Bigas
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Yanan
authors: Y
authors: Li
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Ping
authors: P
authors: Chang
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Yixiang
authors: Y
authors: Mao
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Manal M
authors: MM
authors: Hassan
authors: Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Nanjing, China.
authors: Fangyu
authors: F
authors: Wang
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Donghui
authors: D
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D055354:Exosomes / Q000235:genetics*; D005260:Female; D006801:Humans; D000073890:Liquid Biopsy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012008:Recurrence
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs
keywords: Illumina RNA sequencing; colon cancer; exosome; microRNA; qRT-PCR