title: Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B.
abstract: OBJECTIVE
  Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.
  
  
  METHODS
  A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168.
  
  
  RESULTS
  Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively.
  
  
  CONCLUSIONS
  The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.
authors.affiliation: *Selayang Hospital, Lebuhraya Selayang-Kepong, Batu Caves, Selangor Darul Ehsan †GeneNews (Malaysia) Sdn. Bhd., Mount Miriam Cancer Hospital, Tanjung Bungah **Island Hospital, Penang §Sultanah Bahiyah Hospital, Jalan Langgar, Alor Setar, Kedah ∥Queen Elizabeth Hospital, Kota Kinabalu, Sabah ¶Umum Kuching Sarawak Hospital, Jalan Tun Ahmad Zaidi Adruce, Kuching, Sarawak #Penang Hospital, Jalan Residensi ††Lam Wah Ee Hospital, Pulau Pinang ‡‡GeneNews Diagnostics, Office/Lab 9, Biotechnology Incubation Centre, Technology Park Malaysia, Kuala Lumpur, Malaysia ‡GeneNews Ltd., Richmond Hill, ON, Canada §§Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Haniza
authors.initials: H
authors.lastname: Omar
authors.forename: Chun Ren
authors.initials: CR
authors.lastname: Lim
authors.forename: Samuel
authors.initials: S
authors.lastname: Chao
authors.forename: Michelle Mei Lin
authors.initials: MM
authors.lastname: Lee
authors.forename: Chin Wei
authors.initials: CW
authors.lastname: Bong
authors.forename: Edie Jian Jiek
authors.initials: EJ
authors.lastname: Ooi
authors.forename: Choon Geok
authors.initials: CG
authors.lastname: Yu
authors.forename: Soek Siam
authors.initials: SS
authors.lastname: Tan
authors.forename: Muhammad Radzi
authors.initials: MR
authors.lastname: Abu Hassan
authors.forename: Jayaram
authors.initials: J
authors.lastname: Menon
authors.forename: Raman
authors.initials: R
authors.lastname: Muthukaruppan
authors.forename: Mandeep
authors.initials: M
authors.lastname: Singh
authors.forename: Nik Azim
authors.initials: NA
authors.lastname: Nik Abdullah
authors.forename: Boon Phoe
authors.initials: BP
authors.lastname: Ooi
authors.forename: Robert Phooi Huat
authors.initials: RP
authors.lastname: Ding
authors.forename: Eng Joo
authors.initials: EJ
authors.lastname: Low
authors.forename: Francis
authors.initials: F
authors.lastname: Tan
authors.forename: David
authors.initials: D
authors.lastname: Novak
authors.forename: David F
authors.initials: DF
authors.lastname: Harris
authors.forename: Hengxuan
authors.initials: H
authors.lastname: Yang
authors.forename: Ismail
authors.initials: I
authors.lastname: Merican
authors.forename: Choong-Chin
authors.initials: CC
authors.lastname: Liew
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D030541:Databases, Genetic; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm