PMID- 36753968
OWN - NLM
STAT- MEDLINE
DCOM- 20230223
LR  - 20230223
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 252
DP  - 2023 Mar 1
TI  - Identification of key genes in hepatocellular carcinoma associated with exposure 
      to TCDD and alpha-endosulfan by WGCNA.
PG  - 114595
LID - S0147-6513(23)00099-4 [pii]
LID - 10.1016/j.ecoenv.2023.114595 [doi]
AB  - 2,3,7,8-tet-rachlorodibenzo-p-dioxin (TCDD) and alpha-endosulfan are two typical 
      persistent organic pollutants (POPs), both of which accumulate in the liver and 
      have potential carcinogenic hepatic effects. The underlying molecular mechanisms 
      of pathogenesis of hepatocellular carcinoma (HCC) remain elusive when exposure to 
      POPs. The aim of this study is to explore the key genes involved in HCC when 
      exposure to TCDD and alpha-endosulfan by weighted gene co-expression network analysis 
      (WGCNA). First, we performed co-expressed analysis on HCC and normal condition, 
      based on WGCNA. In results, seven co-expressed modules were identified from 56 
      human liver samples, and the brown module correlated with five stages of HCC. 
      Subsequently, we predicted that human five liver diseases were associated with 
      exposure to TCDD and/or alpha-endosulfan by Nextbio analysis. Functional enrichment 
      analysis showed that the brown module enriched in oxidation-reduction process, 
      DNA replication, oxidoreductase activity and aging, which were the same as the 
      results when exposure to the mixture of TCDD and alpha-endosulfan. Lastly, based on 
      the protein-protein interaction network, we identified three novel genes 
      including HK2, EXO1 and PFKP as key genes in HCC associated with exposure to TCDD 
      and alpha-endosulfan mixture. In addition, survival analysis of key genes in 
      Kaplan-Meier plotter demonstrated that aberrant expression levels of all the 
      three key genes were associated with poor prognosis of HCC. Finally, Western blot 
      analysis confirmed that protein expression levels of PFKP and HK2 in the three 
      exposed groups were significantly elevated, while EXO1 were significantly 
      upregulated when exposure to TCDD and alpha-endosulfan mixture in HepaRG cells. This 
      study provides a new perspective to the understanding of the genetic mechanism of 
      HCC when exposure to POPs.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lu, Yanyuan
AU  - Lu Y
AD  - Institute of Environmental Systems Biology, Environment Science and Engineering 
      College, Dalian Maritime University, Linghai Road 1, Dalian 116026, China.
FAU - Liu, Shiqi
AU  - Liu S
AD  - Institute of Environmental Systems Biology, Environment Science and Engineering 
      College, Dalian Maritime University, Linghai Road 1, Dalian 116026, China.
FAU - Sun, Yeqing
AU  - Sun Y
AD  - Institute of Environmental Systems Biology, Environment Science and Engineering 
      College, Dalian Maritime University, Linghai Road 1, Dalian 116026, China.
FAU - Zhao, Bin
AU  - Zhao B
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing 
      Road 18, Beijing 100085, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Institute of Environmental Systems Biology, Environment Science and Engineering 
      College, Dalian Maritime University, Linghai Road 1, Dalian 116026, China. 
      Electronic address: jotan1995@dlmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230206
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - OKA6A6ZD4K (Endosulfan)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Environmental Pollutants)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Hepatocellular/genetics/metabolism
MH  - Endosulfan
MH  - *Polychlorinated Dibenzodioxins/toxicity
MH  - *Liver Neoplasms/chemically induced/genetics/metabolism
MH  - Gene Expression Profiling/methods
MH  - *Environmental Pollutants/toxicity
OTO - NOTNLM
OT  - Hepatocellular carcinoma
OT  - Hub genes
OT  - TCDD
OT  - WGCNA
OT  - alpha-endosulfan
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/02/09 06:00
MHDA- 2023/02/25 06:00
CRDT- 2023/02/08 18:18
PHST- 2022/08/04 00:00 [received]
PHST- 2023/01/14 00:00 [revised]
PHST- 2023/01/30 00:00 [accepted]
PHST- 2023/02/09 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2023/02/08 18:18 [entrez]
AID - S0147-6513(23)00099-4 [pii]
AID - 10.1016/j.ecoenv.2023.114595 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2023 Mar 1;252:114595. doi: 10.1016/j.ecoenv.2023.114595. 
      Epub 2023 Feb 6.