PMID- 30755830
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220331
IS  - 2167-8359 (Print)
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 7
DP  - 2019
TI  - Identification of special key genes for alcohol-related hepatocellular carcinoma 
      through bioinformatic analysis.
PG  - e6375
LID - 10.7717/peerj.6375 [doi]
LID - e6375
AB  - BACKGROUND: Alcohol-related hepatocellular carcinoma (HCC) was reported to be 
      diagnosed at a later stage, but the mechanism was unknown. This study aimed to 
      identify special key genes (SKGs) during alcohol-related HCC development and 
      progression. METHODS: The mRNA data of 369 HCC patients and the clinical 
      information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 
      patients with certain HCC-related risk factors were included for analysis and 
      divided into seven groups according to the risk factors. Survival analyses were 
      applied for the HCC patients of different groups. The patients with hepatitis B 
      virus or hepatitis C virus infection only were combined into the HCC-V group for 
      further analysis. The differentially expressed genes (DEGs) between the HCCs with 
      alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma 
      package in R with cutoff criteria vertical linelog2 fold change (logFC)|>1.0 and p < 0.05. The 
      DEGs between eight alcohol-related HCCs and their paired normal livers of 
      GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a 
      built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 
      0.05. The intersection of the two sets of DEGs was considered SKGs which were 
      then investigated for their specificity through comparisons between HCC-A and 
      other four HCC groups. The SKGs were analyzed for their correlations with HCC-A 
      stage and grade and their prognostic power for HCC-A patients. The expressional 
      differences of the SKGs in the HCCs in whole were also investigated through Gene 
      Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated 
      through Oncomine database analysis. RESULTS: Pathological stage is an independent 
      prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC 
      patients with other risk factors. Ten SKGs were identified and nine of them were 
      confirmed for their differences in paired samples of HCC-A patients. Three 
      (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) 
      confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 
      had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage 
      and grade. The SKGs each was differentially expressed between HCC-A and at least 
      one of other HCC groups. CD5L was identified to be favorable prognostic factor 
      for overall survival while CSMD1 unfavorable prognostic factor for disease-free 
      survival for HCC-A patients and HCC patients in whole. Through Oncomine database, 
      the dysregulations of the SKGs in HCC and their clinical significance were 
      confirmed. CONCLUSION: The poor prognosis of HCC-A patients might be due to their 
      later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, 
      SLC22A10, UROC1, and SPP2) might play important roles in HCC development, 
      especially alcohol-related HCC development and progression. CD5L might be useful 
      for overall survival and CSMD1 for disease-free survival predication in HCC, 
      especially alcohol-related HCC.
FAU - Zhang, Xiuzhi
AU  - Zhang X
AUID- ORCID: 0000-0002-8080-8135
AD  - Henan Medical College, Zhengzhou, China.
FAU - Kang, Chunyan
AU  - Kang C
AD  - Henan Medical College, Zhengzhou, China.
FAU - Li, Ningning
AU  - Li N
AD  - Henan Medical College, Zhengzhou, China.
FAU - Liu, Xiaoli
AU  - Liu X
AD  - Henan Province People's Hospital, Zhengzhou, China.
FAU - Zhang, Jinzhong
AU  - Zhang J
AD  - Henan Medical College, Zhengzhou, China.
FAU - Gao, Fenglan
AU  - Gao F
AD  - Henan Medical College, Zhengzhou, China.
FAU - Dai, Liping
AU  - Dai L
AD  - Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, 
      Zhengzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190206
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
PMC - PMC6368834
OTO - NOTNLM
OT  - Alcohol-related hepatocellular carcinoma
OT  - Bioinformatic analysis
OT  - CD5L
OT  - CSMD1
OT  - Prognosis
COIS- The authors declare that they have no competing interests.
EDAT- 2019/02/14 06:00
MHDA- 2019/02/14 06:01
PMCR- 2019/02/06
CRDT- 2019/02/14 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2018/12/31 00:00 [accepted]
PHST- 2019/02/14 06:00 [entrez]
PHST- 2019/02/14 06:00 [pubmed]
PHST- 2019/02/14 06:01 [medline]
PHST- 2019/02/06 00:00 [pmc-release]
AID - 6375 [pii]
AID - 10.7717/peerj.6375 [doi]
PST - epublish
SO  - PeerJ. 2019 Feb 6;7:e6375. doi: 10.7717/peerj.6375. eCollection 2019.