Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort.

IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Saumya Madushani Samarasinghe, Asanka Sudeshini Hewage, Rohan Chaminda Siriwardana, Kamani Hemamala Tennekoon, Madunil Anuk Niriella, Sumadee De Silva, Visula Abeysuriya
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引用次数: 0

Abstract

Background: Single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes were reported to be strongly associated with non-alcoholic fatty liver disease (NAFLD) pathogenicity among different populations. We investigated whether these SNPs are associated with prognostic factors and genetic biomarkers of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) in the Sri Lankan context.

Methods: We conducted an exploratory study to evaluate the prevalence of five SNPs (PNPLA3 rs738409, PNPLA3 rs2281135, PNPLA3 rs2294918, TM6SF2 rs58542926 and MBOAT7 rs641738) as genetic risk factors for NASH-HCC pathogenicity. We genotyped 48 NASH-HCC patient samples collected at a clinical setting using a minisequencing method. Impact of each SNP with tumor prognostic factors such as nodularity, tumor size and AFP (alpha-feto protein) level was analyzed using chi square test. We also analyzed the expression of micro RNA-122 (miR-122) in serum and leukocyte telomere length via quantitative real-time PCR. Associations between each SNP with micro RNA-122 (miR-122) expression level and leukocyte telomere length of NASH-HCC patients were analyzed using one-way analysis of variance (ANOVA) test and independent t test. Relationships among tested SNPs and some well-established HCC risk factors such as age, BMI, gender, diabetes status and the cirrhotic stage were also analyzed using chi square test, independent t-test and One-way ANOVA test.

Results: Our analyses demonstrated significant associations between PNPLA3 rs2281135 variant and tumor nodularity. Also, PNPLA3 rs2281135 and PNPLA3 rs2294918 variants were significantly associated with miR-122 expression levels of NASH-HCC patients. Further, age and body mass index (BMI) were significantly associated with PNPLA3 rs2281135 variant in our study cohort.

Conclusion: We found that in the Sri Lankan NASH-related HCC cohort, some PNPLA3 variants (rs2281135 and rs2294918) correlate with tumor nodularity, higher miR-122 expression, and distinct demographic features such as age and BMI. Our work highlights the role of specific SNPs in tumor aggressiveness, contributing to the precision screening for HCC in NASH patients.

斯里兰卡nash相关HCC队列中PNPLA3、TM6SF2和MBOAT7基因单核苷酸多态性与肿瘤侵袭性标志物的相关性
背景:据报道,patatin-like phospholipase domain containing protein 3 (PNPLA3)、跨膜6超家族成员2 (TM6SF2)和膜结合o -酰基转移酶domain containing 7 (MBOAT7)基因的单核苷酸多态性(snp)与不同人群的非酒精性脂肪肝(NAFLD)致病性密切相关。我们研究了这些snp是否与斯里兰卡非酒精性脂肪性肝炎(NASH)相关肝细胞癌(HCC)的预后因素和遗传生物标志物相关。方法:我们开展了一项探索性研究,评估5个snp (PNPLA3 rs738409、PNPLA3 rs2281135、PNPLA3 rs2294918、TM6SF2 rss58542926和MBOAT7 rs641738)作为NASH-HCC致病性遗传危险因素的患病率。我们使用微测序方法对48例临床收集的NASH-HCC患者样本进行基因分型。采用卡方检验分析各SNP与肿瘤结节性、肿瘤大小、甲胎蛋白(AFP)水平等肿瘤预后因素的影响。我们还通过实时荧光定量PCR分析了微RNA-122 (miR-122)在血清和白细胞端粒长度中的表达。采用单因素方差分析(ANOVA)检验和独立t检验分析各SNP与微RNA-122 (miR-122)表达水平和NASH-HCC患者白细胞端粒长度的相关性。采用卡方检验、独立t检验和单因素方差分析分析snp与年龄、BMI、性别、糖尿病状况、肝硬化分期等HCC危险因素的关系。结果:我们的分析表明PNPLA3 rs2281135变异与肿瘤结节性之间存在显著关联。此外,PNPLA3 rs2281135和PNPLA3 rs2294918变体与NASH-HCC患者miR-122表达水平显著相关。此外,在我们的研究队列中,年龄和体重指数(BMI)与PNPLA3 rs2281135变异显著相关。结论:我们发现在斯里兰卡nash相关的HCC队列中,一些PNPLA3变异(rs2281135和rs2294918)与肿瘤结节性、miR-122的高表达以及年龄和BMI等明显的人口统计学特征相关。我们的工作强调了特定snp在肿瘤侵袭性中的作用,有助于精确筛查NASH患者的HCC。
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来源期刊
BMC Gastroenterology
BMC Gastroenterology 医学-胃肠肝病学
CiteScore
4.20
自引率
0.00%
发文量
465
审稿时长
6 months
期刊介绍: BMC Gastroenterology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of gastrointestinal and hepatobiliary disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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