Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

Zhang, Li; Xu, Kuihua; Liu, Chuanmiao; Chen, Jiasheng

doi:10.1111/hepr.12733

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…The above results have been confirmed in these studies of Chanthra et al [24], Chen et al [32], Lu et al [33] and El Sharkawy et al [34]. Especially, Chanthra et al [24] and Zhang et al [15] pointed out G allele was a risk allele for HCC development. However, Clark et al [29], Kim et al [30] and Chen et al [32] replication result for rs7574865 showed no association with risk of HCC.…”

Section: Discussionsupporting

confidence: 59%

“…Up to now, there is no STAT3 gene polymorphism meta-analysis investigating above-mentioned association. These meta-analysises about STAT4 polymorphism [14,4,15] only clarifies the relationship with risk of HCC, without chronic HBV infection, and the samples are small. Therefore, we performed a meta-analysis to evaluate the association between the two SNPs ( STAT3, STAT4 ) and HBV infection and CHB-related HCC.…”

Section: Introductionmentioning

confidence: 99%

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Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Shi

Ojha

et al. 2019

Bioscience Reports

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Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Shi

Ojha

et al. 2019

Bioscience Reports

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“…STAT1 and STAT2 were demonstrated to decrease the growth capacity of HepG2 cells via increased expression stimulated by phosphatidyl-ethanolamine (56). The rs7574865 polymorphism in STAT4 was found to be a risk factor for HCC in a meta-analysis (57). Additionally, somatic mutation of JAK2 was found to be associated with a number of hematologic tumors (58,59), while gain-of-function JAK2 mutations are involved in myeloproliferative malignancies (60).…”

Section: Discussionmentioning

confidence: 99%

Analysis of clinical significance and prospective molecular mechanism of main elements of the JAK/STAT pathway in hepatocellular carcinoma

Wang

Liao

et al. 2019

Int J Oncol

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Hepatocellular carcinoma (HCC) is one the most common malignancies and has poor prognosis in patients. The aim of the present study is to explore the clinical significance of the main genes involved in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in HCC. GSE14520, a training cohort containing 212 hepatitis B virus-infected HCC patients from the Gene Expression Omnibus database, and data from The Cancer Genome Atlas as a validation cohort containing 370 HCC patients, were used to analyze the diagnostic and prognostic significance for HCC. Joint-effect analyses were performed to determine diagnostic and prognostic significance. Nomograms and risk score models were constructed to predict HCC prognosis using the two cohorts. Additionally, molecular mechanism analysis was performed for the two cohorts. Prognosis-associated genes in the two cohorts were further validated for differential expression using reverse transcription-quantitative polymerase chain reaction of 21 pairs of hepatitis B virus-infected HCC samples. JAK2, TYK2, STAT3, STAT4 and STAT5B had diagnostic significance in the two cohorts (all area under curves >0.5; P≤0.05). In addition, JAK2, STAT5A, STAT6 exhibited prognostic significance in both cohorts (all adjusted P≤0.05). Furthermore, joint-effect analysis had advantages over using one gene alone. Molecular mechanism analyses confirmed that STAT6 was enriched in pathways and terms associated with the cell cycle, cell division and lipid metabolism. Nomograms and risk score models had advantages for HCC prognosis prediction. When validated in 21 pairs of HCC and non-tumor tissue, STAT6 was differentially expressed, whereas JAK2 was not differentially expressed. In conclusion, JAK2, STAT5A and STAT6 may be potential prognostic biomarkers for HCC. JAK2, TYK2, STAT3, STAT4 and STAT5B may be potential diagnostic biomarkers for HCC. STAT6 has a role in HCC that may be mediated via effects on the cell cycle, cell division and lipid metabolism.

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“…STAT4, a member of the STAT family, is an important transcription factor that regulates the expression of various molecules in vivo, and mediates cell proliferation, apoptosis, metastasis and other processes (35)(36)(37). In recent years, numerous studies have shown that single nucleotide polymorphisms of STAT4 are closely associated with the occurrence and development of liver cancer (38,39). The present study used TargetScan, PicTar, microRNA and other biological information software to predict that STAT4 may be a common target gene of miR-200a and miR-141.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑200a and microRNA‑141 have a synergetic effect on the suppression of epithelial‑mesenchymal transition in liver cancer by targeting STAT4

et al. 2020

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MicroRNAs (miRNAs or miRs) are non-coding small RNAs that target specific messenger RNAs to inhibit protein translation. miR-200a and miR-141 function as tumor suppressors by targeting STAT4. These two miRNAs belong to the same family, and their expression is often decreased in various cancer types, but are located on different chromosomes of the human genome. The present study showed that the expression levels of miR-141 and miR-200a in serum and cells of liver cancer are significantly downregulated. The expression levels of miR-141 and miR-200a are closely associated with clinicopathological features of liver cancer, especially metastasis and invasion. It is first reported that STAT4 is the new common target gene of miR-141 and miR-200a. In the present study, miR-141 and miR-200a were confirmed to inhibit the expression of E-cadherin and vimentin synergistically during epithelial-mesenchymal transition to regulate the proliferation, migration and invasion of liver cancer cells by targeting STAT4. Simultaneous overexpression of miR-200a and miR-141 resulted in stronger effects compared with each miRNA alone. In addition, overexpression of STAT4 significantly reversed the tumor suppressive roles of miR-200a and miR-141 in liver cancer cells. These findings enrich the tumor suppressor mechanisms of the miR-200 family, and may also provide new experimental and theoretical basis for the use of miRNAs for early diagnosis, prognosis and thorough treatment of liver cancer.

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Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

Abstract: A significantly increased risk of HCC associated with the rs7574865 G was found. The rs7574865 polymorphism might be used as one risk factor for HCC.

Cited by 11 publications

References 31 publications

Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Analysis of clinical significance and prospective molecular mechanism of main elements of the JAK/STAT pathway in hepatocellular carcinoma

MicroRNA‑200a and microRNA‑141 have a synergetic effect on the suppression of epithelial‑mesenchymal transition in liver cancer by targeting STAT4

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