Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair

Guilin, China

Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair

Guilin, China
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Ma M.,Huazhong University of Science and Technology | Hua S.,Huazhong University of Science and Technology | Li G.,Huazhong University of Science and Technology | Wang S.,Huazhong University of Science and Technology | And 6 more authors.
Oncotarget | Year: 2017

Hypoxia-inducible factors (HIFs) are key regulators in oxygen homeostasis. Their stabilization and activity are regulated by prolyl hydroxylase domain (PHD)-1, -2, -3 and factor inhibiting HIF (FIH). This study investigated the relation between these oxygen sensors and the clinical behaviors and prognosis of hepatocellular carcinoma (HCC). Tissue microarray and RT-PCR analysis of tumor tissues and adjacent non-tumor liver tissues revealed that mRNA and protein levels of both PHD3 and FIH were lower within tumors. The lower expression of PHD3 in tumor was associated with larger tumor size, incomplete tumor encapsulation, vascular invasion and higher Ki-67 LI (p < 0.05). The lower expression of FIH in tumor was associated with incomplete tumor encapsulation, vascular invasion, as well as higher TNM stage, BCLC stage, microvascular density and Ki- 67 LI (p < 0.05). Patients with reduced expression of PHD3 or FIH had markedly shorter disease-free survival (DFS), lower overall survival (OS), or higher recurrence (p < 0.05), especially early recurrence. Patients with simultaneously reduced expression of PHD3 and FIH exhibited the least chance of forming tumor encapsulation, highest TNM stage (p < 0.0083), lowest OS and highest recurrence rate (p < 0.05). Multivariate analysis indicated that a lower expression of FIH independently predicted a poor prognosis in HCC. These findings indicate that downregulation of PHD3 and FIH in HCC is associated with more aggressive tumor behavior and a poor prognosis. PHD3 and FIH may be potential therapeutic targets for HCC treatment.


Liao W.,Guilin Medical University | Liao W.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | Huang G.,Guilin Medical University | Liao Y.,Centers for Disease Control and Prevention | And 8 more authors.
Oncotarget | Year: 2014

This study aimed to investigate KIF18A expression in hepatocellular carcinoma (HCC) and to determine the possibility of KIF18A expression being a biomarker in HCC diagnosis or being an independent predictor of disease-free survival (DFS) and overall survival (OS) in HCC patients underwent surgical resection. KIF18A mRNA was detected in 216 cases of HCC tissues by quantitative real-time PCR (qRT-PCR) and in 20 cases of HCC tissues by semi-quantitative RT-PCR. KIF18A protein was determined in 32 cases of HCC tissues by immunohistochemistry (IHC). The survival probability was analyzed by Kaplan-Meier method, and survival curves between groups were obtained by using the log-rank test. Independent predictors associated with DFS were analyzed with Stepwise Cox proportional hazard models. High KIF18A mRNA level was detected in 154 out of 216 (71.3%) cases of HCC. The positive rate of KIF18A expression was significantly higher in liver cancer tissues than that in adjacent normal liver tissues (ANLT) from HCC patients [65.6% (21 of 32) vs. 25.0% (8 of 32), P=0.001]. The KIF18A expression level had positive relevance to the alpha-fetoprotein (AFP) (≥200 ng/ml), tumor size (≥5cm), clinical tumor-node-metastasis (TNM) stage and portal vein tumor thrombus (PVTT) in HCC (all P <0.05). A survival analysis indicated that HCC patients with higher KIF18A expression had a significantly shorter DFS and OS after resection. A multivariate analysis suggested that KIF18A upregualtion was an independent factor for DFS [hazard risk (HR)=1.602; 95% confidence interval (CI), 1.029-2.579; P=0.031] and OS (HR=1.682; 95% CI, 1.089-2.600; P=0.019). KIF18A might be a biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection.


Liao W.,Guilin Medical University | Liao W.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | Wang Y.,Guilin Medical University | Wang Y.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | And 5 more authors.
Medicine (United States) | Year: 2016

Effective biomarkers for predicting prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy is urgently needed. The purpose of this study is to evaluate the value of the preoperative peripheral aspartate aminotransferase to white blood cell count ratio (AWR) for the prognostication of patients with HCC. Clinical data of 396 HCC patients who underwent radical hepatectomy were retrospectively analyzed. The patients were divided into the low-AWR group (AWR ≤5.2) and the high-AWR group (AWR>5.2); univariate analysis, Kaplan-Meier method analysis, and the multivariate analysis by Cox regression were conducted, respectively. The results showed that AWR was associated with alpha-fetoprotein (AFP), tumor size, Barcelona clinic liver cancer (BCLC) stage, portal vein tumor thrombus (PVTT), and alanine aminotransferase (ALT) in HCC. AWR>5.2, AFP>100ng/mL, size of tumor>6cm, number of multiple tumors, B-C of BCLC stage, PVTT, and distant metastasis were predictors of poorer disease-free survival (DFS) and overall survival (OS). Except for recurrence, which was an independent predictor for OS only, AWR>5.2, size of tumor>6cm, and PVTT were independent predictors of both DFS and OS. We concluded that preoperative AWR>5.2 was an adverse predictor of DFS and OS in HCC after hepatectomy, AWR might be a novel prognostic biomarker in HCC after curative resection. © 2016 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | Medical University of South Carolina, Jilin University, Guilin Medical University and Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair
Type: Journal Article | Journal: Oncotarget | Year: 2015

Ubiquitin-specific protease 22 (USP22) removes ubiquitin from histones, thus regulating gene transcription. The expression frequency and expression levels of USP22 were significantly higher in hepatocellular carcinoma (HCC) than in normal liver tissues. High USP22 expression in HCC was significantly correlated with clinical stage and tumor grade. Kaplan-Meier analysis showed that elevated USP22 expression predicted poorer overall survival and recurrence-free survival. High USP22 expression was also associated with shortened survival time in patients at advanced tumor stages and with high grade HCC. Multivariate analyses revealed that USP22 expression is an independent prognostic parameter in HCC. These findings provide evidence that high USP22 expression might be important in tumor progression and serves as an independent molecular marker for poor HCC prognosis. Thus, USP22 overexpression identifies patients at high risk and represents a novel therapeutic molecular target for this tumor.


Zhu Q.,Nanjing Medical University | Kang J.,Nanjing Medical University | Miao H.,Nanjing Medical University | Feng Y.,Nanjing Medical University | And 8 more authors.
FEBS Journal | Year: 2014

It has been reported that the effect of inflammatory cytokines on β-cell destruction in type 1 diabetes is concentration-dependent. However, the underlying mechanisms remain unclear. In the present study, we found that a high concentration of cytokines promoted apoptosis in the rat β-cell line INS-1, whereas a low concentration of cytokines had no effect. We also found that cytokines at a low concentration stimulated neutral ceramidase (NCDase) release via exosomes from INS-1 cells, whereas cytokines at a high concentration inhibited NCDase release. Furthermore, the results showed that the NCDase-containing exosomes isolated from the culture medium of INS-1 cells treated with cytokines at a low concentration inhibited apoptosis induced by a high concentration of cytokines. Finally, the results also showed that the protective action of NCDase in the exosomes on apoptosis was mediated by the generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 2. Taken together, these findings revealed a novel NCDase-S1P- phosphate-S1P receptor 2-dependent mechanism by which a low level of inflammatory cytokines protects pancreatic β-cells from apoptosis induced by a high level of inflammatory cytokines. © 2014 FEBS.


Liao W.,Guilin Medical University | Liao W.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | Zhang J.,Medical University of South Carolina | Zhu Q.,Nanjing Medical University | And 12 more authors.
Translational Oncology | Year: 2014

BACKGROUND: Preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cutoff value of NLR in several studies is not consistent. This study aims to investigate the correlation of preoperative NLR with clinicopathologic features and the prognosis in patients who have undergone resection for HCC. METHODS: Clinical data of 256 patients with HCC who underwent radical hepatectomy were retrospectively analyzed. The patients were divided into the low-NLR group (NLR ≤ 2.31) and the high-NLR group (NLR N 2.31). A univariate analysis was performed to assess clinicopathologic characteristics that influenced disease-free survival (DFS) and overall survival (OS) in patients. The significant variables were further analyzed by a multivariate analysis using Cox regression. The Kaplan-Meier method was used to assess the DFS and OS rate. RESULTS: The value of NLR was associated with tumor size, clinical tumor-node-metastasis (TNM) stage, portal vein tumor thrombus (PVTT), distant metastasis, and aspartate aminotransferase (AST) in HCC. NLR N 2.31, size of tumor N 5 cm, number of multiple tumors, III-IV of TNM stage, PVTT, distant metastasis, and AST N 40 U/l were predictors of poorer DFS and OS. NLR N 2.31, size of tumor N 5 cm, III-IV of TNM stage, and AST N 40 U/l were independent predictors of DFS and OS. CONCLUSION: Preoperative NLR N 2.31 was an adverse predictor of DFS and OS in HCC after hepatectomy. This study suggested that NLR might be a novel prognostic biomarker in HCC after curative resection. © 2014 Neoplasia Press. All rights reserved.


Cheng X.,Huazhong University of Science and Technology | He S.,Guilin Medical University | He S.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | Yuan J.,Huazhong University of Science and Technology | And 6 more authors.
Free Radical Biology and Medicine | Year: 2016

A fundamental element of acute lung injury (ALI) is the inflammation that is part of the body's immune response to a variety of local or systemic stimuli. Lipoxins (LXs) are important endogenous lipids that mediate resolution of inflammation. Previously, we demonstrated that LXA4 reduced the LPS inhalation-induced pulmonary edema, neutrophil infiltration and TNF-α production in mice. With the same model, the current investigation focused on the role of the airway epithelium, a first-line barrier and a prime target of inhaled toxicants. We report that LXA4 strongly inhibited LPS-induced ALI in mice, in part by protecting the airway epithelium and preserving the E-cadherin expression and airway permeability. Using a cryo-imaging assay and fluorescence detection, LXA4 was shown to block LPS-induced ROS generation and preserve mitochondrial redox status both in vivo and in vitro. To further assess whether and how NF-E2-related factor 2 (Nrf2) was involved in the protective effect of LXA4, fluorescence resonance energy transfer (FRET) analysis was employed in human epithelial cell line (16HBE), to determine the relative distance between Nrf2 and its negative regulator or cytosolic inhibitor, Kelch-like ECH-associated protein 1 (Keap1). It provided us the evidence that LXA4 further promoted the dissociation of Nrf2 and Keap1 in LPS-treated 16HBE cells. The results also showed that LXA4 activates Nrf2 by phosphorylating it on Ser40 and triggering its nuclear translocation. Moreover, when the plasmid expression dominant negative mutation of Nrf2 was transfected as an inhibitor of wild-type Nrf2, the protective effect of LXA4 on E-cadherin expression was almost completely blocked. These results provide a new mechanism by which LXA4 inhibits LPS-induced ALI through Nrf2-mediated E-cadherin expression. © 2016 Elsevier Inc. All rights reserved.


Yuan S.-G.,Guilin Medical University | Yuan S.-G.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | Liao W.-J.,Guilin Medical University | Liao W.-J.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair | And 6 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (≥4cm), alpha-fetoprotein (≥100ng/ml), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041- 2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01- 2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.


Yang J.-J.,Guilin Medical University | Hu Z.-G.,Guilin Medical University | Shi W.-X.,Guilin Medical University | Deng T.,Guilin Medical University | And 3 more authors.
World Journal of Gastroenterology | Year: 2015

AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer. METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters. RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009). CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.


PubMed | Guilin Medical University and Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair
Type: Journal Article | Journal: Oncology letters | Year: 2016

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.

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