Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma

Yamashita, Taro; Kitao, Azusa; Matsui, Osamu; Hayashi, Takuo; Nio, Kouki; Kondo, Masanari; Ohno, Naoki; Miyati, Tosiaki; Okada, Hikari; Mizukoshi, Eishiro; Honda, Masao; Nakanuma, Yasuni; Takamura, Hiroyuki; Ohta, Tetsuo; Nakamoto, Yasunari; Yamamoto, Masakazu; Takayama, Tadatoshi; Arii, Shigeki; Wang, Xin Wei

doi:10.1002/hep.27093

Cited by 107 publications

(129 citation statements)

References 38 publications

(53 reference statements)

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…Several studies have been engaged in searching for candidate biomarkers for the treatment and prognosis predition of HCC, identifying AFP, miRNA and long non-coding RNAs as potential biomarkers (32,33). In the present study, among the 276 HCC patients enrolled, UBE2A expression was increased in the cancer tissues compared with the adjacent normal tissues.…”

Section: Discussionmentioning

confidence: 63%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21.0 software. UBE2A mRNA and protein were highly expressed in HCC tissues compared with those in the adjacent normal tissue. Immunohistochemical analysis revealed that UBE2A protein was more strongly stained in the 276 paraffin-embedded HCC tissues as compared with the 63 adjacent normal tissue. Statistical analysis also demonstrated that UBE2A expression was significantly associated with histological differentiation, TNM stage and vascular invasion of HCC (P<0.05). Notably, HCC patients with a high expression of UBE2A had a shorter survival time as compared with those with a low expression of UBE2A. There results suggested that UBE2A may be involved in the pathogenesis of HCC and may serve as an important prognostic marker.Further exploration of the involvement of UBE2A in HCC development may provide novel therapeutic targets. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide and the fifth most common cancer type (1). HCC is a global health burden and its prevalence varies worldwide (2). The incidence rate is reported to be higher in Asia (>20 cases/100,000 individuals) in comparison with that in North America and Europe (<5 cases/100,000 individuals) (3). The prognosis of HCC is poor, as evident by the fact that the number of annual mortality cases (~600,000) is almost equal to the number of new cases diagnosed annually (4). The median rate for 1-year survival is 80% (range, 63-97%), for 3-year survival is 70% (range, 34-78%) and for 5-year survival is 50% (range, 17-69%) (5). Surgery remains the most important treatment strategy for patients with HCC. The 5-year survival rate of patients with early HCC subsequent to resection treatment reaches 50%, although these patients exhibit a high recurrence rate (6,7). Despite advances in the diagnosis (8) and treatment (9) of HCC, the prognosis of this disease remains poor (10). Therefore, further clarification of the mechanisms underlying its development is important (11,12).At present, the prognosis of HCC is predicted based on imaging findings and biomarkers. Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited. Consequently, there is an urgency to develop a novel biomarker for the prognosis of HCC.The ubiquitin system serves a ...

show abstract

Section: Discussionmentioning

confidence: 63%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…For immunohistochemical analyses, HCC tissues and adjacent non-cancerous liver tissues were obtained from 144 patients who had undergone a hepatectomy from 2002 to 2012 at Kanazawa University Hospital, Japan. The pathological diagnoses were performed as previously described [12]. Of these HCC specimens, 38 were obtained fresh and snap-frozen in liquid nitrogen for RNA analysis.…”

Section: Clinical Hcc Specimensmentioning

confidence: 99%

“…Various molecular profiling approaches have been used to identify potential therapeutic targets which are specifically activated in HCC [4][5][6][7][8]. Some studies have indicated the importance of evaluating ''stemness'' in HCC; it reflects the malignant nature of the tumor and closely correlates with a poor prognosis after surgery [9][10][11][12]. Recent evidence has also suggested that HCC may conform to the cancer stem cell (CSCs) hypothesis, which proposes that a subset of cells with stem cell features play a fundamental role in tumor maintenance and chemo/radiation resistance [13].…”

Section: Introductionmentioning

confidence: 99%

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Nio

Yamashita

Okada

et al. 2015

Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

Background & Aims: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM + liver cancer stem cells. Methods: Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. Results: CHD4 was abundantly expressed in EpCAM + hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM + liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model.Conclusions: CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Ó

show abstract

“…The mean SI of the 3 areas was defined as the SI of the background liver (mean ROI, 334.2 « 103.0 mm 2 ; range, 218.8 to 577.8 mm 2 ). We calculated the SI ratio in the HBP by dividing the SI of the tumor by the SI of the background liver 8,12 and divided the patients into a high intensity group and a low intensity group by their median ratios.…”

Section: Image Analysismentioning

confidence: 99%

“…5,6 The molecular correlation of the uptake of gadoxetic acid by HCCs, as well as the expression of OATP1B3, with the maintenance of mature hepatocyte function and good prognosis was recently reported. 8 Indeed, in surgically resected cases, hyperintense HCCs in the HBP showed less aggressive biological behavior or more favorable outcome than hypointense HCCs. 9 -13 Hyperintense HCCs also appear to be susceptible to transcatheter arterial chemolipiodolization (TACE).…”

Section: Introductionmentioning

confidence: 98%

Significance of the Signal Intensity of Gadoxetic Acid-enhanced MR Imaging for Predicting the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma

et al. 2016

View full text Add to dashboard Cite

Purpose: We attempted to clarify the relationship between the signal intensity (SI) in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the efficacy of hepatic arterial infusion chemotherapy (HAIC) in hepatocellular carcinomas (HCCs).Methods: We enrolled 14 patients with HCCs who underwent gadoxetic acid-enhanced MR imaging prior to HAIC using cisplatin and 5-fluorouracil. In the hepatobiliary phase, we calculated the SI of the HCCs and the background liver. In cases with multiple HCCs, we calculated the SI of the largest lesion. Patients were classified into high (n = 7) and low intensity (n = 7) groups based on the median value of the SI ratio (SI of the tumor/SI of the background liver). We analyzed progression-free survival using the Kaplan-Meier method and the log-rank test. In the 5 patients with a history of HCC surgery, we compared the expression of immunohistochemical organic anion-transporting polypeptide (OATP) 8 between the high and low intensity groups by chi-square test.Results: The SI ratios were 0.568 « 0.093 (mean « standard deviation) in the high intensity group and 0.251 « 0.086 in the low intensity group. Compared to the group with low signal intensity, the group with high signal intensity demonstrated significantly lower serum levels of alpha fetoprotein (AFP) (P = 0.0350), significantly higher progressionfree survival (P = 0.0108), better differentiation of tumor grade at histologic examination (P = 0.0253), and significantly higher OATP8 expression (P = 0.0253).Conclusion: Patients with HCCs of high SI ratio in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging can respond better to HAIC.

show abstract

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma

Cited by 107 publications

References 38 publications

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Significance of the Signal Intensity of Gadoxetic Acid-enhanced MR Imaging for Predicting the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma

Contact Info

Product

Resources

About