title: Pretreatment MicroRNA Level and Outcome in Sorafenib-treated Hepatocellular Carcinoma.
abstract: Sorafenib represents the first effective targeted therapy for advanced stage hepatocellular carcinoma (HCC); however, adequate patient stratification regarding sorafenib-responsiveness is still missing. Our aim was to analyse the association between the pretreatment microRNA profile of HCC and patient survival under sorafenib treatment. Total RNA was extracted from diagnostic fine-needle aspiration biopsy (FNAB) cytological smears of 20 advanced stage HCC patients collected between June 2008 and July 2012. All patients underwent sorafenib administration after FNA. Clinicopathological and survival data were recorded. Fourteen frequently deregulated miRNAs in HCC (miR-17-5p, miR-18a, miR-21, miR-34a, miR-122, miR-195, miR-210, miR-214, miR-221, miR-222, miR-223, miR-224, miR-140, miR-328) were tested by qRT-PCR. NormFinder software was used to select proper miR (mir-140) as a reference. Satisfactory amount of total RNA was obtained from all the considered samples (mean 10.8 ± 9.3 µg, range 0.2-32.2 µg). Among the analysed miRNAs, high miR-214 expression was associated with smaller tumor size (p=0.019), whereas high miR-17-5p expression correlated with better Eastern Cooperative Oncology Group performance status (p=0.003). The survival analysis revealed that high miR-224 expression was associated with increased progression-free and overall survival (PFS p=0.029; OS p=0.012). Pretreatment microRNA profiling, especially miR-224 expression, might serve as an ancillary tool for the better assessment of expected survival rates for patients under sorafenib treatment.
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Benedek
authors.initials: B
authors.lastname: Gyöngyösi
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Éva
authors.initials: É
authors.lastname: Végh
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Balázs
authors.initials: B
authors.lastname: Járay
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Eszter
authors.initials: E
authors.lastname: Székely
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: György
authors.initials: G
authors.lastname: Bodoky
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF).
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Schaff
authors.affiliation: Second Department of Pathology, Semmelweis University, Budapest, Hungary (BG, BJ, ES, ZS, AK)MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary (ZS)Department of Oncology, United Saint Stephen and Saint Laslo Hospital and Outpatient Clinics, Budapest, Hungary (ÉV, GB)ARC-NET Research Centre, Department of Pathology and Diagnostic, Policlinico GB Rossi, University of Verona, Verona, Italy (MF) kiss.andras@med.semmelweis-univ.hu.
authors.forename: András
authors.initials: A
authors.lastname: Kiss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: FNAB; hepatocellular carcinoma; microRNA; sorafenib; survival