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Open AccessArticle

Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma

1
Division of Hepatology and Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung 80249, Taiwan
2
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
4
School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
5
Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
6
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
7
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 20401, Taiwan
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Department of Pharmacy, FooYin University Hospital, Pingtung 92847, Taiwan
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Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
10
Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
11
TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
*
Authors to whom correspondence should be addressed.
Lan-Ting Yuan and Jer-Hwa Chang made an equal contribution to this work.
J. Clin. Med. 2019, 8(9), 1406; https://doi.org/10.3390/jcm8091406
Received: 25 July 2019 / Revised: 26 August 2019 / Accepted: 3 September 2019 / Published: 6 September 2019
(This article belongs to the Special Issue Molecular Mechanisms of Cancer Chemoprevention)
The long noncoding (lnc)RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), plays a crucial role in the development of hepatocellular carcinoma (HCC). However, potential genetic variants (single nucleotide polymorphisms, SNPs) in MALAT1 that affect the susceptibility and progression of HCC have rarely been explored. Three tagging SNPs, viz., rs3200401 C > T, rs619586 A > G, and rs1194338 C > A, in MALAT1 were genotyped by a TaqMan allelic discrimination assay in 394 HCC patients and 1199 healthy controls. A stratified analysis showed that younger patients (<55 years) with the MALAT1 rs619586 G allele had a decreased risk of HCC under a codominant model (AOR = 0.289, 95% CI: 0.108–0.773, p = 0.013) and dominant model (AOR = 0.286, 95% CI: 0.107–0.765, p = 0.013). Female patients and patients with a smoking habit who carried the CA + AA genotype of rs1194338 had a lower risk of developing vascular invasion (p = 0.049) and a high Child–Pugh grade (B or C) (p = 0.036), respectively. Under the dominant model, smokers with the MALAT1 rs3200401 CT + TT genotype had a higher frequency of hepatitis B virus (HBV) infection (p = 0.034). Moreover, the aspartate aminotransferase was higher in patients with the rs3200401 CT + TT genotype. Furthermore, analyses of clinical datasets revealed that MALAT1 expression level was gradually unregulated during HCC development from normal liver, cirrhotic liver, dysplastic liver to HCC and correlated with poor survival rates in HCC patients, especially in the hepatitis virus-infected population. View Full-Text
Keywords: long noncoding RNA; metastasis-associated lung adenocarcinoma transcript 1; single nucleotide polymorphisms; susceptibility; clinicopathologic characteristics; hepatocellular carcinoma long noncoding RNA; metastasis-associated lung adenocarcinoma transcript 1; single nucleotide polymorphisms; susceptibility; clinicopathologic characteristics; hepatocellular carcinoma
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MDPI and ACS Style

Yuan, L.-T.; Chang, J.-H.; Lee, H.-L.; Yang, Y.-C.; Su, S.-C.; Lin, C.-L.; Yang, S.-F.; Chien, M.-H. Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma. J. Clin. Med. 2019, 8, 1406.

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