title: Diagnosis of HCC for patients with cirrhosis using miRNA profiles of the tumor-surrounding tissue - A statistical model based on stepwise penalized logistic regression.
abstract: The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver. The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76μkat/l, B: 1.02μkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC.
authors.affiliation: Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany; University of Leipzig, Visceral, Transplant, Thoracic, and Vascular Surgery, Germany. Electronic address: haluk.morgul@gmail.com.
authors.forename: Mehmet Haluk
authors.initials: MH
authors.lastname: Morgul
authors.affiliation: University of Leipzig, Visceral, Transplant, Thoracic, and Vascular Surgery, Germany; Harzklinikum Dorothea Christiane Erxleben GmbH, Clinic for Traumatology, Hand and Orthopedic Surgery, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Klunk
authors.affiliation: PAREXEL International GmbH, Berlin, Germany.
authors.forename: Zografia
authors.initials: Z
authors.lastname: Anastasiadou
authors.affiliation: Private Statistical Office, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gauger
authors.affiliation: University of Leipzig, Visceral, Transplant, Thoracic, and Vascular Surgery, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Dietel
authors.affiliation: Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Reutzel-Selke
authors.affiliation: General, Visceral, and Vascular Surgery, University of Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Felgendref
authors.affiliation: University of Leipzig, Visceral, Transplant, Thoracic, and Vascular Surgery, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Hau
authors.affiliation: General, Visceral, and Vascular Surgery, University of Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Tautenhahn
authors.affiliation: Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Rosa Bianca
authors.initials: RB
authors.lastname: Schmuck
authors.affiliation: Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Raschzok
authors.affiliation: Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Igor Maximillian
authors.initials: IM
authors.lastname: Sauer
authors.affiliation: University of Leipzig, Visceral, Transplant, Thoracic, and Vascular Surgery, Germany; General and Visceral Surgery, Helios Park-Klinikum Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics; D003663:Decision Trees; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000235:genetics; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015233:Models, Statistical; D012313:RNA / Q000302:isolation & purification
chemical_list: D035683:MicroRNAs; D012313:RNA
keywords: Biomarkers; HCC; Stepwise penalized logistic regression; Transplantation; Tumor associated cirrhosis