Combination of serum RASSF1A methylation and AFP is a promising non-invasive biomarker for HCC patient with chronic HBV infection

Dong, Xiaotian; He, Hui; Zhang, Weiying; Yu, Daojun; Wang, Xianjun; Chen, Yueming

doi:10.1186/s13000-015-0317-x

Cited by 33 publications

(37 citation statements)

References 21 publications

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“…Although serum AFP level has been widely used for diagnosis of HCC, the sensitivity and specificity of AFP for HCC are limited (21). Therefore, it is urgent to identify novel potential biomarkers for early prognosis and monitoring of tumor recurrence, which is helpful for clinicians to select therapeutic strategies, so that the prognosis of HCC patients may be improved.…”

Section: Rhamm Mrna Clinical ----------------------------------------mentioning

confidence: 99%

Upregulation of hyaluronan-mediated motility receptor in hepatocellular carcinoma predicts poor survival

Liao

Li³

et al. 2015

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common types of cancer across the world. Hyaluronic acid (HA) has been reported to serve an important role in tumor extension, progression, migration and invasion. In addition, the receptor for HA-mediated motility (RHAMM) has been demonstrated to be overexpressed in different types of cancer. However, whether the upregulation of RHAMM contributes to hepatocarcinogenesis of HCC remains unclear. The present study examined the RHAMM expression in 187 HCC patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). RHAMM expression was significantly upregulated in liver cancer tissues compared with that observed in adjacent normal liver tissues. The IHC analysis demonstrated that RHAMM was overexpressed in 18 (72.0%) of the 25 HCC tissues. Furthermore, overexpression of RHAMM was associated with tumor-node-metastasis (TNM), the presence of vascular invasion and recurrence. Notably, the present study indicated that the overexpression of RHAMM was closely associated with the shorter disease-free and overall survival, so it may be a potential independent predictor for disease-free and overall survival of HCC patients. In conclusion, the upregulation of RHAMM is associated with HCC progression and prognosis; and it may be a potential independent predictor of disease-free and overall survival of HCC following surgical resection. IntroductionLiver cancer is one of the most common neoplasms worldwide, and hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and accounts for 70-85% of all cases (1), ranking the sixth most common malignant tumors worldwide (2). More than 600,000 people lose their lives due to HCC every year (3), and HCC is the third most frequent cause of cancer-associated mortality (4). Previous studies have demonstrated that the incidence rate of HCC has been increasing. Surgical resection and liver-transplantation are superior therapeutic methods for HCC compared with other treatments, including radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and chemotherapy, the treatment outcomes remain unsatisfactory owing to the high recurrence rate and high fatality rate of HCC (2). If HCC was detected and diagnosed earlier, surgical resection and liver-transplantation would result in an improved curative effect, therefore improving the disease-free and overall survival. The serum levels of α-fetoprotein (AFP) and ultrasonography (US) are widely used to screen for and assess HCC throughout the world. However, the sensitivity and specificity of AFP for HCC diagnosis and surveillance have certain limitations; US depends on the operator's skill, and clinicians are not always able to distinguish HCC clearly from other nodules (5). Consequently, novel potential serum biomarkers are required for prognosis and metastatic recurrence of HCC.Hyaluronic acid (HA) is an extracellular matrix (ECM) polymer and is frequently localized in the stroma of solid tumors, which is s...

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Section: Rhamm Mrna Clinical ----------------------------------------mentioning

confidence: 99%

Upregulation of hyaluronan-mediated motility receptor in hepatocellular carcinoma predicts poor survival

Liao

Li³

et al. 2015

Oncology Letters

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“…Apart from the selection of the detection technique and thresholds, the determination of the precise genomic positions of those CpG dinucleotides analyzed is also of great importance [82]. With regards to clinical heterogeneity, only 20.5% (9/44) of our enrolled articles mentioned the presence or absence of preoperative treatment [38,40,41,45,47,50,53,55]. Some studies suggested that both radiotherapy and chemotherapy can alter a patient's DNA methylation status; therefore, the type of preoperative treatment performed should be clari ed [83,84].…”

Section: Discussionmentioning

confidence: 99%

Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

Xing

Xiao

et al. 2020

Preprint

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Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial. Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC. Results: Forty-four articles involving 4,777 cases were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses. Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

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“… 38 , 39 But serum level of AFP was still frequently used for the diagnosis of HBV-relative HCC with considerable sensitivity and specificity in the People’s Republic of China. 40 In the meta-analysis of AFP and STAT4 expression, only three studies (including the current study) with 327 cases were included. 14 , 27 No relationship was found between AFP and STAT4 in the studies of Wubetu et al 14 and Wang et al 27 The relationship between STAT4 and AFP needs to be illuminated.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of STAT4 in hepatocellular carcinoma and its effect on cell growth and apoptosis

Liang

Liu

et al. 2016

OTT

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BackgroundRecent studies showed that signal transducer and activator of transcription 4 (STAT4) was downregulated in hepatocellular carcinoma (HCC) tissues. However, the role of STAT4 in HCC is still unknown. The aim of this study is to explore the association between STAT4 expression and other clinicopathological features in HCC and to test the effect of STAT4 on cell growth and apoptosis in vitro.MethodsSTAT4 was evaluated by immunohistochemistry in 171 HCC and corresponding paraneoplastic liver, 37 cirrhosis, and 33 normal liver tissues. Association between STAT4 and clinicopathological parameters was analyzed. Meta-analysis on STAT4 in cancer was performed. The effect of STAT4 small interfering RNA (siRNA) on cell growth and cell apoptosis was also detected.ResultsPositive rate of STAT4 was 29.2% (50/171) in HCC tissues, 53.2% (91/171) in paraneoplastic liver tissues, 64.9% (24/37) in cirrhosis tissues, and 72.7% (24/33) in normal liver tissues. STAT4 was upregulated in younger patients who were female, with single tumor node, early TNM stage, without portal vein tumor embolus, and α-fetoprotein (AFP)-positive tumors compared with the groups comprising older patients, males, and those with multiple tumor nodes, advanced TNM stage, with portal vein tumor embolus, and AFP negative tumors. Meta-analysis showed STAT4 was correlated with TNM stage (OR =0.50, 95% CI =0.30, 0.83, P=0.008) and age (OR =0.58, 95% CI =0.38, 0.95, P=0.032) in malignant tissues, and with AFP level (OR =1.76, 95% CI =1.06, 2.94, P=0.03) in HCC. STAT4 siRNA promoted growth and suppressed apoptosis of HepG2 cells.ConclusionSTAT4 might play a vital role in development of HCC, via influencing cell growth and apoptosis, as a tumor suppressor.

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Combination of serum RASSF1A methylation and AFP is a promising non-invasive biomarker for HCC patient with chronic HBV infection

Cited by 33 publications

References 21 publications

Upregulation of hyaluronan-mediated motility receptor in hepatocellular carcinoma predicts poor survival

Upregulation of hyaluronan-mediated motility receptor in hepatocellular carcinoma predicts poor survival

Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

Clinicopathological significance of STAT4 in hepatocellular carcinoma and its effect on cell growth and apoptosis

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