Qiang Gao

Fudan University, Shanghai, Shanghai Shi, China

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Publications (54)334.41 Total impact

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    ABSTRACT: Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. Understanding the molecular pathogenesis of HCC recurrence and metastasis is the key to improve patients' prognosis. In this study, we report that protein tyrosine phosphatase receptor S (PTPRS) is significantly downregulated in nearly 80% of HCCs, and its expression negatively correlates with aggressive pathological features, like larger tumor size and advanced stage. In addition, PTPRS deficiency is independently associated with shorter survival and increased recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous expression of PTPRS. Restoration of wild-type but not mutant PTPRS expression significantly inhibits HCC cell migration and invasion in vitro as well as lung metastasis in vivo, while knockdown of its expression significantly promotes invasion and metastasis. Notably, PTPRS-regulated HCC invasiveness is accompanied by typical changes of epithelial-mesenchymal transition. Moreover, PTPRS forms a complex with epithermal growth factor receptor (EGFR) and regulates its tyrosine residues' phosphorylation. Ectopic expression of EGFR reverses the metastasis inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting phosphorylation of key molecules in EGFR downstream pathways re-inhibits EMT and metastasis caused by PTPRS downregulation. Meanwhile, promoter hypermethylation of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a de-methylation agent 5-Aza-CdR recovers PTPRS expression in a dose-dependent manner. These findings suggest that epigenetic inactivation of PTPRS may increase the phosphorylation and activity of EGFR signaling to promote EMT and metastasis in HCC. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 05/2015; DOI:10.1002/hep.27911 · 11.19 Impact Factor
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    ABSTRACT: A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20-1.36, P < 0.001; dominant model: OR = 1.27, 95 % CI = 1.16-1.38, P < 0.001; recessive model: OR = 1.59, 95 % CI = 1.36-1.85, P < 0.001). Furthermore, increased risks for HCC were also revealed in stratified analyses by ethnicity, sample size, and quality scores of cohorts as well as variation type, functional impact, and protein domain location of polymorphisms. In conclusion, the present meta-analysis suggested that the presence of MDR1 mutant alleles might be a risk factor for HCC.
    Tumor Biology 04/2015; DOI:10.1007/s13277-015-3407-1 · 3.61 Impact Factor
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    ABSTRACT: Atypical chemokine receptors (ACRs) have been discovered to participate in the regulation of tumor behavior. Here, we reported a tumor suppressive role of a novel ACR member, CC chemokine receptor like 1 (CCRL1), in human hepatocellular carcinoma (HCC). Both mRNA and protein expressions of CCRL1 correlated with malignant phenotype of HCC cells and were significantly down-regulated in tumor tissue compared with paired normal liver tissue. In both the initial and validation cohorts (n = 240 and 384, respectively), CCRL1 deficiency was associated with advanced tumor stage and was an independent index for worse survival and increased recurrence. Furthermore, knockdown or forced expression of CCRL1 revealed that CCRL1 suppressed the proliferation and invasion of HCC cells in vitro and reduced tumor growth and lung metastasis in vivo, with depressed levels of CCL19 and CCL21. By sequestrating CCL19 and CCL21, CCRL1 reduced their binding to CCR7 and consequently mitigated the detrimental impact of CCR7, including Akt/GSK-3β pathway activation and nuclear accumulation of β-catenin in tumor cells. Clinically, the prognostic value of the CCR7 expression in HCC depended on the expression level of CCRL1, suggesting that CCRL1 may serve as an upstream switch for the CCR7 signaling cascade. Together, our findings suggest that CCRL1 impairs chemotactic events that associated with CCR7 in progression and metastasis of HCC. Our results also show a potential interplay between typical and atypical chemokine receptors in human cancer.
    The Journal of Pathology 03/2015; 235(4). DOI:10.1002/path.4450 · 7.43 Impact Factor
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    ABSTRACT: Neddylation-Cullin-RING E3 ligase (CRL) pathway has recently been identified as a potential oncogenic event and attractive anticancer target; however, the underlying mechanisms of it have not been well elucidated. In this study, RhoB, a well-known tumor suppressor, was identified and validated with iTRAQ-based quantitative proteomic approach as a new target of this pathway in liver cancer cells. Specifically, Cullin 2-RBX1 E3 ligase that requires NEDD8 conjugation for its activation interacted with RhoB and promoted its ubiquitination and degradation. In human liver cancer tissues, the neddylation-CRL pathway was over-activated and reversely correlated with RhoB levels. Moreover, RhoB accumulation upon the inhibition of neddylation-CRL pathway for anticancer therapy contributed to the induction of tumor suppressors p21 and p27, apoptosis and growth suppression. Our findings highlight the degradation of RhoB via neddylation-CRL pathway as an important molecular event that drives liver carcinogenesis and RhoB itself as a pivotal effector for anticancer therapy targeting this oncogenic pathway. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    Molecular &amp Cellular Proteomics 12/2014; 14(3). DOI:10.1074/mcp.M114.045211 · 7.25 Impact Factor
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    ABSTRACT: The identification of prognostic markers for hepatocellular carcinoma (HCC) is needed for clinical practice. Tripartite motif-containing 35 (TRIM35) is a tumor suppressor of HCC. TRIM35 inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells. We found that expression of PKM2 was significantly increased in HCC tissues. This overexpression of PKM2 was correlated with a high TNM stage and level of vascular invasion. Patients with HCC who were positive for PKM2 expression and negative for TRIM35 expression had shorter overall survival and time to recurrence than patients who were negative for PKM2 and positive for TRIM35. Furthermore, PKM2/TRIM35 combination was an independent and significant risk factor for recurrence and survival. In conclusion, PKM2 (+) and TRIM35 (-) contribute to the aggressiveness and poor prognosis of HCC. PKM2/TRIM35 expression could be a biomarker for the prognosis of HCC and target for cancer therapy.
    Oncotarget 12/2014; · 6.63 Impact Factor
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    ABSTRACT: Background Triggering receptors expressed on myeloid cells 1 (TREM-1) is a novel molecule that modulates inflammatory responses. Hepatocellular carcinoma (HCC) is a well-known type of inflammation-related cancer. However, TREM-1 expression and its direct effects on HCC cells have not been previously determined. Methods Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescence were used to detect TREM-1 expression. TREM-1 upregulation by pcDNA (mammalian expression vector with the CMV promoter) and its downregulation by shRNA (short hairpin RNA) were used to determine the function of this molecule. Transwell, CCK-8, cell cycle, and apoptosis assays were used to detect the effects of TREM-1 on HCC cells. Immunohistochemical staining of samples from a cohort of 322 HCC patients was used to determine the prognostic value of TREM-1. Results TREM-1 investigation through Western blot, qRT-PCR, and immunofluorescence analyses revealed that TREM-1 was expressed in HCC cells and tumor tissues. Functional experiments suggested that TREM-1 significantly promoted proliferation, invasion, and inhibited apoptosis of HCC cells. Inflammatory cytokine profiles under TREM-1 up- or downregulation indicated the majority of proinflammation cytokines significantly and positively correlated with TREM-1 expression, including IL-1β, TNF-α, and MCP-1. Western blot analyses revealed that p65, STAT3, ERK, and AKT might be the downstream effectors of TREM-1 signal transduction. High TREM-1 expression correlated significantly with increased recurrence and poorer survival in HCC patients, and it was an independent prognostic factor for recurrence (P = 0.009). Conclusions TREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.
    Annals of Surgical Oncology 12/2014; DOI:10.1245/s10434-014-4191-7 · 3.94 Impact Factor
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    ABSTRACT: The prognosis for hepatocellular carcinoma (HCC) remains dismal in terms of overall survival (OS), and its molecular pathogenesis has not been completely defined. Here, we report that the expression of deubiquitylase USP7 is higher in human HCC tissues than in matched non-tumor tissues. Ectopic USP7 expression promotes the growth of HCC cells in vivo and in vitro. Mechanistically, USP7 overexpression fosters HCC cell growth by forming a complex with and stabilizing the TRIP12 protein, which induces constitutive p14ARF ubiquitination. Clinically, USP7 overexpression is significantly correlated with a malignant phenotype, including larger tumor size, multiple tumor, poor differentiation, elevated α-fetoprotein (AFP), and microvascular invasion. Moreover, overexpression of USP7 and/or TRIP12 correlates with shorter OS and higher cumulative recurrence rates in HCC. Together, our results reveal that USP7 stabilizes TRIP12 by deubiquitination, thus constitutively inactivating p14ARF and promoting HCC progression, and represents a novel marker for predicting prognosis and a potential therapeutic target for HCC. This article is protected by copyright. All rights reserved.
    Hepatology 12/2014; DOI:10.1002/hep.27682 · 11.19 Impact Factor
  • Nature Reviews Gastroenterology &#38 Hepatology 11/2014; DOI:10.1038/nrgastro.2014.6-c1 · 10.81 Impact Factor
  • Nature Reviews Clinical Oncology 11/2014; DOI:10.1038/nrclinonc.2014.122-c1 · 15.70 Impact Factor
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    ABSTRACT: RYBP is a member of the polycomb group (PcG) proteins that typically act as transcriptional repressors via epigenetic modification of chromatin. The present study was designed to investigate the role of RYBP in HCC progression, chemosensitivity, and patient survival, and to explore the underlying molecular mechanism(s). In this study we investigated the expression of RYBP in 400 pairs of human HCC tissues and matched noncancerous samples. The effects of RYBP on HCC tumor growth and metastasis and chemosensitivity were determined both in vitro and in vivo. We herein demonstrate that the RYBP expression in HCC tissue samples was significantly lower than that in matched noncancerous liver tissues. Clinically, the low expression of RYBP was an independent predictor of a poor prognosis in patients with HCC. In in vitro HCC models, enforced RYBP expression inhibited cell growth and invasion, induced apoptosis, and increased the chemosensitivity of the cells, while RYBP knockdown led to the opposite effects. Furthermore, RYBP expression was induced by cisplatin, and adenovirus-mediated RYBP expression inhibited HCC tumor growth and sensitized HCC to conventional chemotherapy in vivo. Our results demonstrate that reactivating RYBP in cancer cells may provide an effective and safe therapeutic approach to HCC therapy.
    Oncotarget 10/2014; 5(22). · 6.63 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):LB-223-LB-223. DOI:10.1158/1538-7445.AM2014-LB-223 · 9.28 Impact Factor
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    ABSTRACT: Background Metastasis accounts for the most deaths in patients with hepatocellular carcinoma (HCC). Receptor activator of nuclear factor kappa B ligand (RANKL) is associated with cancer metastasis, while its role in HCC remains largely unknown. Methods Immunohistochemistry was performed to determine the expression of RANK in HCC tissue (n = 398). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to examine the expression of RANK, E-cadherin, N-cadherin, vimentin, Snail, Slug, Twist and MMPs in HCC cells. Wound healing and Transwell assays were used to evaluate cell migration and invasion ability. Results We found that expression of RANK, the receptor of RANKL, was significantly higher in HCC tumor tissues than in peritumor liver tissues (p<0.001). Constitutive expression of RANK was detected in HCC cell lines, which can be up-regulated when HCC cells were stimulated with RANKL. Notably, in vitro experiments showed that activation of RANKL-RANK axis significantly promoted migration and invasion ability of HCC cells. In addition, RANKL stimulation increased the expression levels of N-cadherin, Snail, and Twist, while decreased the expression of E-cadherin, with concomitant activation of NF-κB signaling pathway. Moreover, administration of the NF-κB inhibitor attenuated RANKL-induced migration, invasion and epithelial-mesenchymal transition of HCC cells. Conclusions RANKL could potentiate migration and invasion ability of RANK-positive HCC cells through NF-κB pathway-mediated epithelial-mesenchymal transition, which means that RANKL-RANK axis could be a potential target for HCC therapy.
    PLoS ONE 09/2014; 9(9):e108507. DOI:10.1371/journal.pone.0108507 · 3.53 Impact Factor
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    ABSTRACT: Therapeutic intervention in neddylation pathway is an emerging area for cancer treatment. Herein, we evaluated the clinical relevance and therapeutic potential of targeting this pathway in intrahepatic cholangiocarcinoma (ICC). Immunohistochemistry of neddylation pathway components in a cohort of 322 cases showed that E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human ICC. Notably, NAE1 was identified as an independent prognosticator for postoperative recurrence (P=0.009) and a combination of NEDD8 and NAE1 provided a better power for predicting patient clinical outcomes. In vitro treatment with MLN4924, a small-molecule NEDD8-activating enzyme inhibitor, led to a dose-dependent decrease of viability in both established and primary cholangiocarcinoma cell lines. Additionally, MLN4924 exhibited at least additive effect when combined with cisplatin. By blocking cullins neddylation, MLN4924 inactivated Cullin-Ring ligase (CRL) and caused the accumulation of CRL substrates that triggered cell cycle arrest, senescence or apoptosis. Meanwhile, MLN4924 was well-tolerated and significantly inhibited tumor growth in xenograft model of cholangiocarcinoma. Taken together, our findings indicated that upregulated neddylation pathway was involved in ICC progression and interference in this pathway could be a promising target for ICC therapy.
    Oncotarget 08/2014; 5(17). · 6.63 Impact Factor
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    ABSTRACT: Background A number of oncoproteins and tumor suppressors are known to be neddylated, but whether the neddylation pathway is entirely activated in human cancer remains unexplored. Methods NEDD8-activating enzyme (NAE) (E1) and NEDD8-conjugating enzyme (E2) expression and global-protein neddylation were examined by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction analysis. Cell proliferation, clonogenic survival, migration, and motility in vitro, as well as tumor formation and metastasis in vivo, were determined upon neddylation inhibition by MLN4924, an investigational NEDD8-activating enzyme inhibitor. Survival was analyzed with Kaplan-Meier methods and compared by the log-rank test. All statistical tests were two-sided. Results The entire neddylation pathway, including NEDD8-activating enzyme E1, NEDD8-conjugating enzyme E2, and global-protein neddylation, is overactivated in both lung adenocarcinoma and squamous-cell carcinoma. Compared with lung adenocarcinoma patients with low expression, those with high expression had worse overall survival (NEDD8-activating enzyme E1 subunit 1 [NAE1]: hazard ratio [HR] = 2.07, 95% confidence interval [CI] = 0.95 to 4.52, P = .07; ubiquitin-conjugating enzyme E2M (UBC12): HR = 13.26, 95% CI = 1.77 to 99.35, P = .01; global protein neddylation: HR = 3.74, 95% CI = 1.65 to 8.47, P = .002). Moreover, inhibition of neddylation by the NAE inhibitor MLN4924 statistically significantly suppressed proliferation, survival, migration, and motility of lung cancer cells in vitro and tumor formation and metastasis in vivo. At the molecular level, MLN4924 inactivated Cullin-RING E3 ligases, led to accumulation of tumor-suppressive Cullin-RING E3 ligase substrates and induced phorbol-12-myristate-13-acetate-induced protein 1 (NOXA)-dependent apoptosis or cellular senescence. Conclusions Our study highlights the overactivated neddylation pathway in lung cancer development and as a promising therapeutic target.
    JNCI Journal of the National Cancer Institute 06/2014; 106(6). DOI:10.1093/jnci/dju083 · 15.16 Impact Factor
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    ABSTRACT: Virus-induced hepatocarcinogenesis involves a series of histological developmental processes with the step-wise acquisition of several genetic changes that are necessary for the malignant transformation of hepatocytes. Although genetic alterations are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC), little is known about the contributions of specific genes to this process. To gain insight into the genetic alterations involved in the neoplastic evolution from chronic hepatitis B virus infection to dysplastic nodules (DN) to HCC, we captured and sequenced the exomes of four DNA samples: one DN sample, two HCC samples and one control peripheral blood sample from a single HCC patient. Mutations in the UBE3C gene (encoding ubiquitin ligase E3C) were observed in both tumor tissues. Then, we resequenced the UBE3C gene in a cohort of 105 HCC patients and identified mutations in 17 out of total 106 (16.0%) HCC patients. The subsequent experiments showed that UBE3C promoted HCC progression by regulating HCC cells epithelial-mesenchymal transition. Clinically, a tissue microarray study of a cohort containing 323 HCC patients revealed that the overexpression of UBE3C in primary HCC tissues correlated with decreased survival (hazard ratio [HR] = 1.657, 95% confidence interval [CI] = 1.220-2.251, P = 0.001) and early tumor recurrence (HR = 1.653, 95% CI = 1.227-2.228, P = 0.001) in postoperative HCC patients. Conclusion: Our findings indicate that UBE3C is a candidate oncogene involved in tumor development and progression and therefore a potential therapeutic target in applicable HCC patients. (Hepatology 2014;).
    Hepatology 06/2014; DOI:10.1002/hep.27012 · 11.19 Impact Factor
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    ABSTRACT: Background & Aims Pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second-most common hepatic cancer, is a poorly understood and its incidence is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. Methods We performed whole-exome sequencing of 7 paired ICCs and their surrounding, non-tumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and non-tumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients, and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). Results Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples, and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4/7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1/9 PTP genes; 41.1% had mutations in PTPN3.Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3L232R and PTPN3L384H, which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 had altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than non-tumor tissues had higher rates of disease recurrence than patients without. Conclusions Using whole-exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence in patients.
    Gastroenterology 05/2014; 146(5). DOI:10.1053/j.gastro.2014.01.062 · 13.93 Impact Factor
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    ABSTRACT: We previously identified JWA as a novel microtubule-associated protein (MAP), which is implicated in carcinogenesis and tumor progression. The aims of the present study were to investigate the biological action and the prognostic significance of JWA in hepatocellular carcinoma (HCC). Quantitative real-time PCR and Western blot were used to detect JWA mRNA and protein expression, respectively, in stepwise metastatic HCC cell lines and HCC tissues. Short hairpin RNA was used to inhibit JWA expression in HCC cells. The effects of JWA depletion on cell migration, invasion, adhesion and in vivo metastasis were investigated. Immunohistochemistry of JWA was conducted in microarrays with tissue from 314 HCC patients who had undergone surgical resection. Prognostic significance was assessed using the Kaplan-Meier method and log-rank tests. The result showed JWA expression was decreased in the highly metastatic HCC cell lines and HCC tissues. Depletion of JWA caused a notable increase in cell migration, invasion and adhesion in vitro and metastasis in vivo. Furthermore, there was an inverse correlation between JWA expression and FAK expression and phosphorylation, RhoA activation and matrix metalloproteinase-2 (MMP-2) activity in HCC cells. More notably, multivariate analysis revealed that a low level of JWA expression was an independent prognosticator for both recurrence-free and overall survival for HCC patients after surgical resection, especially for AFP-normal HCC patients. Taken together, our data demonstrate that JWA plays a crucial role in HCC progression and suggest JWA may be a potential prognostic biomarker and therapeutic target for HCC. © 2012 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 04/2014; 53(4). DOI:10.1002/mc.21981 · 4.77 Impact Factor
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    ABSTRACT: Expression of heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) has been reported to be dysregulated in tumors but its specific contributions to tumor formation and progression are not fully understood. Here, we demonstrate that hnRNPAB is overexpressed in highly metastatic cells and tumor tissues from hepatocellular carcinoma (HCC) patients with recurrence. We found that hnRNPAB overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. RNAi-mediated silencing of the EMT factor Snail attenuated hnRNPAB-enhanced cell invasion in vitro and lung metastasis in vivo. Mechanistically, HnRNPAB acted to transactivate Snail transcription, which in turn inhibited transcription of the pivotal Snail target gene E-cadherin. Overexpression of hnRNPAB in HCC samples correlated with higher Snail levels, shorter overall survival and higher tumor recurrence. HnRNPAB overexpression, alone or in combination with Snail, was found to be a significant independent risk factor for recurrence and survival after curative resection. In conclusion, our findings define hnRNPAB as an activator of EMT and metastasis in HCC that predicts poor clinical outcomes.
    Cancer Research 03/2014; 74(10). DOI:10.1158/0008-5472.CAN-13-2509 · 9.28 Impact Factor
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    ABSTRACT: Studies have highlighted important features of the nucleocytoplasmic transport of mRNAs and proteins. Nuclear RNA export factor 3 (NXF3) is a member of the nuclear RNA export factor family that plays a role in mediating the export of cellular mRNA from the nucleus to the cytoplasm for translation. However, little is known about the clinical significance of NXF3 in human tumors. To evaluate the prognostic significance of NXF3 in hepatocellular carcinoma (HCC), the expression levels of NXF3 in a cohort of 112 patients with primary HCC who had undergone hepatectomy for histologically confirmed HCC were assessed by immunohistochemistry. It was identified that the expression levels of NXF3 were higher in the primary HCC tissues compared with those in paired peritumoral liver tissues. The overexpression of NXF3 in the HCC tissues was correlated with decreased survival time [hazard ratio (HR) = 1.954, 95% confidence interval (CI) = 1.034-3.695, P=0.039] and earlier tumor recurrence (HR = 2.101, 95% CI = 1.186-3.722, P=0.011) in postoperative patients with HCC. Notably, overexpression of NXF3 was correlated with a poor survival time and increased recurrence following HCC resection in male patients (P=0.020 and P=0.007, respectively) but not in female patients (P=0.916 and P=0.821, respectively). In conclusion, the findings provide evidence that implicates NXF3 as a prospective predictor of HCC prognosis as well as a potential therapeutic target for cancer treatment.
    Oncology letters 03/2014; 7(3):641-646. DOI:10.3892/ol.2014.1809 · 0.99 Impact Factor
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    ABSTRACT: To evaluate the differences in enhancement pattern of hepatocellular carcinoma (HCC) 20 mm or smaller and enhancement effects of hepatic vessels on early dynamic contrast-enhanced magnetic resonance imaging (MRI) obtained with gadoxetic acid and gadopentetate dimeglumine in the same patients with cirrhosis. We reviewed MR images using gadoxetic acid and gadopentetate dimeglumine in the same 34 patients with 42 histologically confirmed HCCs (median diameter, 14.5 mm). The percentage enhancements (PEs) of HCC, the hepatic artery and portal vein and relative contrasts (RCs) between HCC and the liver were calculated and analyzed statistically. The PEs of HCC, the hepatic artery and portal vein were significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p = 0.0256 for HCC, p < 0.0001 for hepatic artery) and portal phase (p < 0.0001 for HCC, portal vein). The RC between HCC and the liver was significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p = 0.0422), but was not significantly different in the portal phase (p = 0.1133). Forty-one of the 42 (97.62 %) nodules showed arterial hypervascularization. Of these, 31 (75.61 %) nodules were hypointense in the portal phase for gadoxetic acid, and 22 (53.66 %) were hypointense for gadopentetate dimeglumine (p = 0.038). Compared with gadopentetate dimeglumine, gadoxetic acid-enhanced MRI demonstrated a different enhancement pattern of inferior arterial enhancement and was more rapidly hypointense in the portal phase for HCC. It showed markedly lower enhancement for hepatic artery and portal vein in the patients with cirrhosis.
    Hepatology International 01/2014; 8(1). DOI:10.1007/s12072-013-9467-7 · 2.47 Impact Factor

Publication Stats

1k Citations
334.41 Total Impact Points


  • 2006–2015
    • Fudan University
      • • Institutes of Biomedical Sciences
      • • Department of Surgery
      Shanghai, Shanghai Shi, China
  • 2011
    • Zhejiang University of Science and Technology
      Hang-hsien, Zhejiang Sheng, China