title: High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.
abstract: Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs.
  
  
  
  In 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery. Twelve patients with incomplete data regarding HCC recurrence, secondary liver transplantation, or perioperative death were excluded, leaving 40 patients with early recurrence <12 months (R+) or without recurrence for >24 months (R-) to compare grading, T, L, V, and R status. If tissue quality permitted, micro RNAs were measured in HCC and liver tissue.
  
  
  
  Ten women and 30 men (64.0 ± 10.2 years) were analyzed. R+ occurred in 29 patients 6.2 ± 4.5 months after resection. Surveillance of R- was 26.2 ± 5.2 months. High intratumoral expression of miR-135a was associated with high risk of recurrence (HR = 4.2, p = 0.024, time to recurrence 8.8 ± 2.0 vs. 24.8 ± 4.4 months in patients with low miR-135a expression). As expected, T3 status was correlated with early recurrence, while other histological parameters and expression of miR-21, miR-122, and miR-125a did not.
  
  
  
  We show a significant association between high expression of miR-135a and early HCC recurrence. Therefore, high intratumoral miR-135a expression might serve as a novel biomarker to identify patients urgently requiring adjuvant therapy post resection.
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. j.von-felden@uke.de.
authors.forename: Johann
authors.initials: J
authors.lastname: von Felden
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Heim
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Kornelius
authors.initials: K
authors.lastname: Schulze
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Department for Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Ewald
authors.affiliation: Department for Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Nashan
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Wege
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; C544965:MIRN135 microRNA, human; D035683:MicroRNAs
keywords: HCC; Liver resection; Recurrence; miRNA