PMID- 26414287
OWN - NLM
STAT- MEDLINE
DCOM- 20160607
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 9
DP  - 2015
TI  - Identification of Circulating Biomarker Candidates for Hepatocellular Carcinoma 
      (HCC): An Integrated Prioritization Approach.
PG  - e0138913
LID - 10.1371/journal.pone.0138913 [doi]
LID - e0138913
AB  - Hepatocellular carcinoma (HCC) is the world's third most widespread cancer. 
      Currently available circulating biomarkers for this silently progressing 
      malignancy are not sufficiently specific and sensitive to meet all clinical 
      needs. There is an imminent and pressing need for the identification of novel 
      circulating biomarkers to increase disease-free survival rate. In order to 
      facilitate the selection of the most promising circulating protein biomarkers, we 
      attempted to define an objective method likely to have a significant impact on 
      the analysis of vast data generated from cutting-edge technologies. Current study 
      exploits data available in seven publicly accessible gene and protein databases, 
      unveiling 731 liver-specific proteins through initial enrichment analysis. 
      Verification of expression profiles followed by integration of proteomic 
      datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 
      previously characterized circulating HCC biomarkers. Finally, interactome 
      analysis of these proteins with midkine (MDK), dickkopf-1 (DKK-1), current 
      standard HCC biomarker alpha-fetoprotein (AFP), its interacting partners in 
      conjunction with HCC-specific circulating and liver deregulated miRNAs target 
      filtration highlighted seven novel statistically significant putative biomarkers 
      including complement component 8, alpha (C8A), mannose binding lectin (MBL2), 
      antithrombin III (SERPINC1), 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), 
      alcohol dehydrogenase 6 (ADH6), beta-ureidopropionase (UPB1) and cytochrome P450, 
      family 2, subfamily A, polypeptide 6 (CYP2A6). Our proposed methodology provides 
      a swift assortment process for biomarker prioritization that eventually reduces 
      the economic burden of experimental evaluation. Further dedicated validation 
      studies of potential putative biomarkers on HCC patient blood samples are 
      warranted. We hope that the use of such integrative secretome, interactome and 
      miRNAs target filtration approach will accelerate the selection of high-priority 
      biomarkers for other diseases as well, that are more amenable to downstream 
      clinical validation experiments.
FAU - Awan, Faryal Mehwish
AU  - Awan FM
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Naz, Anam
AU  - Naz A
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Obaid, Ayesha
AU  - Obaid A
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Ali, Amjad
AU  - Ali A
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Ahmad, Jamil
AU  - Ahmad J
AD  - Research Center for Modeling and Simulation (RCMS), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Anjum, Sadia
AU  - Anjum S
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
FAU - Janjua, Hussnain Ahmed
AU  - Janjua HA
AD  - Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
      Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
LA  - eng
PT  - Journal Article
DEP - 20150928
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MicroRNAs)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteome)
SB  - IM
MH  - Biomarkers, Tumor/*blood
MH  - Carcinoma, Hepatocellular/*blood/genetics
MH  - Databases, Protein
MH  - Disease-Free Survival
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Liver/metabolism/pathology
MH  - Liver Neoplasms/*blood/genetics
MH  - MicroRNAs/genetics/metabolism
MH  - Neoplasm Proteins/blood/metabolism
MH  - Organ Specificity
MH  - Protein Interaction Mapping
MH  - Proteome/metabolism
MH  - ROC Curve
PMC - PMC4586137
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/09/29 06:00
MHDA- 2016/06/09 06:00
PMCR- 2015/09/28
CRDT- 2015/09/29 06:00
PHST- 2015/06/02 00:00 [received]
PHST- 2015/09/06 00:00 [accepted]
PHST- 2015/09/29 06:00 [entrez]
PHST- 2015/09/29 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
PHST- 2015/09/28 00:00 [pmc-release]
AID - PONE-D-15-23568 [pii]
AID - 10.1371/journal.pone.0138913 [doi]
PST - epublish
SO  - PLoS One. 2015 Sep 28;10(9):e0138913. doi: 10.1371/journal.pone.0138913. 
      eCollection 2015.