Abstract
BackgroundGATA family of transcription factors are critical for organ development and associated with progression of various cancer types. However, their expression patterns and prognostic values for hepatocellular carcinoma (HCC) are still largely unknown.MethodsExpression of GATA transcription factors in HCC cell lines and tissues (n = 240) were evaluated by RT-qPCR, western blot and immunohistochemistry. Cellular proliferation, migration and invasion of HepG2 was evaluated by CCK-8 kit, scratch wound assay and transwell matrigel invasion assay, respectively.ResultsGATA2 expression was decreased in HCC cell lines (p = 0.056 for mRNA, p = 0.040 for protein) and tissues (p = 1.27E-25) compared with normal hepatocytes. Decreased expression of intratumoral GATA2 protein significantly correlated with elevated alpha feto-protein (p = 2.7E-05), tumor size >5 cm (p = 0.049), absence of tumor capsule (p = 0.002), poor differentiation (p = 0.005), presence of tumor thrombi (p = 0.005) and advanced TNM stage (p = 0.001) and was associated with increased recurrence rate and decreased overall survival rate by univariate (p = 1.6E-04 for TTR, p = 1.7E-04 for OS) and multivariate analyses (HR = 0.63, 95% CI = 0.43–0.90, p = 0.012 for TTR; HR = 0.67, 95% CI = 0.47–0.95, p = 0.026 for OS). RNAi-mediated knockdown of GATA2 expression significantly enhanced proliferation, migration and invasion of HepG2 cell in vitro.ConclusionsDecreased expression of hematopoietic factor GATA2 was associated with poor prognosis of HCC following resection.
Highlights
Liver cancer is the fifth most common cancer and the second leading cause of cancer death in men worldwide [1]
Our results demonstrated the decreased expression of GATA2 in hepatocellular carcinoma (HCC) cell lines compared with normal hepatocytes as well as in HCC tissues with recurrence compared with those without recurrence
We showed by RT-qPCR that GATA1 mRNA was expressed at relatively low level in majorities of hepatic and HCC cell lines analyzed (22gCt, mean 1.1E-05, range 6.6E-07,6.9E-05, approximately 1000 times less than other GATAs’ expression, Fig. 1A)
Summary
Liver cancer is the fifth (seventh) most common cancer and the second (sixth) leading cause of cancer death in men (women) worldwide [1]. Loss of function of GATA4 , 6 by promoter hypermethylation [13,14,15] or nucleocytoplasmic mislocalization [16,17] is a common event in carcinoma of lung, digestive tract, pancrea and ovarian, which causes loss of expression of epithelial-specific markers (disabled-2, collagen IV and laminin) leading to cellular dedifferentiation and downregulates potential targets of tumor suppressor genes (the trefoil factors, inhibin and disabled-2). GATA family of transcription factors are critical for organ development and associated with progression of various cancer types. Their expression patterns and prognostic values for hepatocellular carcinoma (HCC) are still largely unknown
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