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Dig Dis Sci. 2019 Jan;64(1):123-136. doi: 10.1007/s10620-018-5307-x. Epub 2018 Oct 4.

Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma.

Cho SY1, Kim S2, Son MJ2, Rou WS3,4, Kim SH3,4, Eun HS5,6, Lee BS7,8.

Author information

1
School of Medicine, Chungnam National University, 266, Munwha-ro, Jung-gu, Daejeon, 35015, Republic of Korea.
2
Department of Clinical Research, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea.
3
Department of Internal Medicine, Chungnam National University Hospital, 282, Munwha-ro, Jung-gu, Daejeon, 34952, Republic of Korea.
4
Department of Internal Medicine, School of Medicine, Chungnam National University, 266, Munwha-ro, Jung-gu, Daejeon, 35015, Republic of Korea.
5
Department of Internal Medicine, Chungnam National University Hospital, 282, Munwha-ro, Jung-gu, Daejeon, 34952, Republic of Korea. hyuksoo@cnuh.co.kr.
6
Department of Internal Medicine, School of Medicine, Chungnam National University, 266, Munwha-ro, Jung-gu, Daejeon, 35015, Republic of Korea. hyuksoo@cnuh.co.kr.
7
Department of Internal Medicine, Chungnam National University Hospital, 282, Munwha-ro, Jung-gu, Daejeon, 34952, Republic of Korea. gie001@cnuh.co.kr.
8
Department of Internal Medicine, School of Medicine, Chungnam National University, 266, Munwha-ro, Jung-gu, Daejeon, 35015, Republic of Korea. gie001@cnuh.co.kr.

Abstract

BACKGROUND:

Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized.

AIM:

To investigate the clinical significance of TXNs and TXNDC family members in HCC.

METHODS:

Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed.

RESULTS:

HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes.

CONCLUSIONS:

TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival.

KEYWORDS:

Hepatocellular carcinoma; Overall survival; TXN-domain-containing protein; Thioredoxin

PMID:
30288659
DOI:
10.1007/s10620-018-5307-x
[Indexed for MEDLINE]

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