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1.
Jing Chen Wen-Bin Liu Wei-Dong Jia Ge-Liang Xu Jin-Liang Ma Yun Ren Hao Chen Si-Nan Sun Mei Huang Jian-Sheng Li 《PloS one》2014,9(1)
Background
Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear.Methods
We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters.Results
Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC.Conclusions
Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery. 相似文献2.
Jinpu Yu Xiubao Ren Yongzi Chen Pengpeng Liu Xiyin Wei Hui Li Guoguang Ying Kexin Chen Hans Winkler Xishan Hao 《PloS one》2013,8(2)
Aim
To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC.Methods
The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT) related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) were compared.Results
A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS+ HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036), which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68+ macrophages and more cancer cells displaying EMT features were found in NTS+IL-8+ samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS+IL-8+ HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022). Accordingly, the OS of NTS+IL-8+ HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR) of 3.457.Conclusion
Dysfunctional activation of the NTS/IL-8 pathway was detected in HCC which is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients. 相似文献3.
Fei Liu Yonggang Wei Wentao Wang Kefei Chen Lvnan Yan Tianfu Wen Jichun Zhao Mingqing Xu Bo Li 《PloS one》2012,7(11)
Background
Salvage liver transplantation (SLT) is restricted to patients who develop hepatocellular carcinoma (HCC) recurrence within Milan criteria (MC). Little is known about outcomes for SLT in patients with recurrent HCC within University of California San Francisco (UCSF) criteria after liver resection (LR).Methods
Between January 2001 and December 2011, 380 patients with HCC meeting UCSF criteria, 200 of which were resected (LR group) from a perspective of SLT in case of recurrence, and 180 directly underwent LT (PLT). We compared patient characteristics, perioperative and long-term outcomes between SLT and PLT groups. We also assessed the outcome of LR and PLT groups.Results
Among the 200 patients in LR group, 86 (43%) developed HCC recurrence and 15/86 (17%) of these patients presented HCC recurrence outside UCSF criteria. Only 39 of the 86 patients underwent SLT, a transplantation rate of 45% of patients with HCC recurrence. Compared with PLT group, LR group showed lower overall survival rate (P = 0.005) and higher recurrence rate (P = 0.006). Although intraoperative blood loss and required blood transfusion were more frequent in SLT group, the perioperative mortality and posttransplant complications were similar in SLT and PLT groups. The overall survival and recurrence rates did not significantly differ between the two groups. When stratifying by graft type in the SLT group, overall survival and recurrence rates did not significantly differ between deceased donor LT (DDLT) and living donor LT (LDLT) groups. In the subgroup analysis by MC, similar results were observed between patients with recurrent HCC meeting MC and patients with recurrent HCC beyond MC but within UCSF criteria.Conclusion
Our single institution experience demonstrated that prior hepatectomy and SLT for recurrent HCC within UCSF criteria was feasible and SLT could achieve the same outcome as PLT. 相似文献4.
Shi-Hong Zhang Chan-Juan Wang Ling Shi Xing-Hua Li Jing Zhou Li-Bing Song Wen-Ting Liao 《PloS one》2013,8(6)
Background
The flotillin family member flotillin-1 (FLOT1) encodes a caveolae-associated, integral membrane protein that belongs to lipid raft family and involves in vesicular trafficking and signal transduction. However, the role of FLOT1 in development and progression of cancer remains largely unknown. The present study was aimed to investigate the clinical and prognostic significance of FLOT1 in hepatocellular carcinoma (HCC).Methods
Real-time PCR and western blot analyses were applied to examine FLOT1 expression in fourteen HCC cell lines and one normal hepatic cell line, ten pairs of primary HCC and matched adjacent noncancerous liver tissues from the same patient. Immunohistochemistry (IHC) was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 196 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinical parameters.Results
FLOT1 expression was evidently up-regulated in HCC tissues compared with that in the matched adjacent noncancerous liver tissues. In the 196 cases of tested HCC samples, FLOT1 protein level was positively correlated with Tumor size (P = 0.025), clinical stage (P<0.002), CLIP stage (P<0.001), vascular invasion (P<0.001), relapse (P<0.001), and serum AFP levels (P = 0.025). Patients with higher FLOT1 expression had shorter overall survival time, whereas those with lower FLOT1 expression had longer survival time.Conclusions
Our study demonstrated FLOT1 is associated with aggressive characteristics of HCC, and suggested the possibility of its use as a prognostic marker in patients with HCC. 相似文献5.
Jian-Hong Zhong Hang Li Nan Xiao Xin-Ping Ye Yang Ke Yan-Yan Wang Liang Ma Jie Chen Xue-Mei You Zhi-Yuan Zhang Shi-Dong Lu Le-Qun Li 《PloS one》2014,9(9)
Background & Aims
Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT.Methods
Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT.Results
The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT.Conclusions
HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy. 相似文献6.
Jian-Hong Zhong Bang-De Xiang Wen-Feng Gong Yang Ke Qin-Guo Mo Liang Ma Xing Liu Le-Qun Li 《PloS one》2013,8(7)
Background and Aims
Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE).Methods
A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan–Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model.Results
The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE.Conclusions
LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved. 相似文献7.
Fuzhen Qi Mingde Huang Yun Pan Yao Liu Jibin Liu Juan Wen Kaipeng Xie Hongbing Shen Hongxia Ma Yi Miao Zhibin Hu 《PloS one》2014,9(1)
Background
MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.Methods
The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis.Results
The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) = 0.76,95% confidence intervals (CI) = 0.59–0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR = 0.72, 95% CI = 0.56–0.91, P = 0.007).Conclusions
These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese. 相似文献8.
Chunmei Yang Heehyoung Lee Veronica Jove Jiehui Deng Wang Zhang Xueli Liu Stephen Forman Thanh H. Dellinger Mark Wakabayashi Hua Yu Sumanta Pal 《PloS one》2013,8(1)
Background
Several previous studies have identified a strong association between T-cell infiltration and clinical outcome in ovarian cancer. The role of B-cells remains controversial, however.Methods
Forty-nine paraffin-embedded omental specimens derived from patients with high grade epithelial ovarian cancer were assessed. Immunohistochemical analyses were performed to characterize expression of CD19+ B-cells and pSTAT3 as high (>50% positively staining cells [PSCs]) or low (<50% PSCs). The Kaplan-Meier method with log-rank test was used to determine the association between clinicopathologic parameters and overall survival (OS). A multi-variate Cox proportional hazards regression analysis including nature of debulking (primary vs secondary), histology, tumor grade, receipt of prior chemotherapy, B-cell infiltration and pSTAT3 expression was performed.Results
Median OS was 160.6 months in those patients with low B-cell expression vs 47.3 months in those with high B-cell expression (P = 0.0015). Similarly, median OS was improved in those patients with low pSTAT3 expression (160.6 vs 47.9 months, P = 0.02). In a multivariate model to predict survival, only the degree of B-cell infiltration and clinical stage were retained. pSTAT3 expression did not enter the final model, possibly be due to a high positive correlation with B-cell infiltration (r = 0.82, P<0.0001).Conclusions
Increased B-cell infiltration and pSTAT3 expression in omental tissue are associated with poorer survival. 相似文献9.
10.
Ji Hoon Kim Bo Hwa Sohn Hyun-Sung Lee Sang-Bae Kim Jeong Eun Yoo Yun-Yong Park Woojin Jeong Sung Sook Lee Eun Sung Park Ahmed Kaseb Baek Hui Kim Wan Bae Kim Jong Eun Yeon Kwan Soo Byun In-Sun Chu Sung Soo Kim Xin Wei Wang Snorri S. Thorgeirsson John M. Luk Koo Jeong Kang Jeonghoon Heo Young Nyun Park Ju-Seog Lee 《PLoS medicine》2014,11(12)
Background
Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications.Methods and Findings
Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3–3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1–2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus–positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus.Conclusions
Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors'' Summary 相似文献11.
Sangbin Han Justin Sangwook Ko Sang-Man Jin Hyo-Won Park Jong Man Kim Jae-Won Joh Gaabsoo Kim Soo Joo Choi 《PloS one》2014,9(10)
Background
Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury.Methods
This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury.Results
Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations.Conclusions
Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma. 相似文献12.
Background
Ischemia/reperfusion injury (IRI) is commonly considered to play a crucial role in the pathogenesis of small-for-size syndrome (SFSS) after liver transplantation. Rapid regeneration is also considered essential for the survival of SFS grafts.Methods
Mouse models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Survival rate and serum alanine aminotransferase were observed. IRI was assessed by hepatic pathologic alterations, apoptosis and necrosis. Regeneration response was detected by mitotic index, BrdU incorporation and PCNA, Cyclin D1 and Cyclin E expression. The expression of mTOR, AKT, ERK, JNK2 and p70S6K, also involved in regeneration signaling pathways, were analyzed as well.Results
30% partial liver graft resulted in a significantly low 7-day survival rate (P = 0.002) with no marked difference in tissue injury compared with the 50% partial graft group. Serum alanine aminotransferase levels were not significantly different between partial transplantation and full-size transplantation. Western blot analysis of caspase-3 and TUNEL staining also indicated no significant difference in apoptosis response between 30% partial transplantation and half-size or full-size transplantation (P = 0.436, P = 0.113, respectively). However, liver regeneration response indicators, mitotic index (P<0.0001) and BrdU (P = 0.0022), were markedly lower in 30% LTx compared with 50% LTx. Suppressed expression of PCNA, cyclin D1, cyclin E, mTOR, JNK2, AKT, ERK and p70S6K was also detected by western blot.Conclusions
Liver regeneration is markedly suppressed in SFSS, and is more likely the primary cause of SFSS, rather than ischemia/reperfusion injury. Therapy for recovering graft regeneration could be a potentially important strategy to reduce the incidence of SFSS. 相似文献13.
14.
Qi Zhang Jian Qi Shengping Hou Liping Du Hongsong Yu Qingfeng Cao Yan Zhou Dan Liao Aize Kijlstra Peizeng Yang 《PloS one》2014,9(5)
Background
Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS).Methods
A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry.Results
The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10−7, OR = 1.54; Pc = 3.83×10−8, OR = 1.40; Pc = 6.35×10−4, OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype.Conclusions
The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production. 相似文献15.
Rong-Zhen Luo Pei-Qiang Cai Mei Li Jia Fu Zhi-Yi Zhang Jie-Wei Chen Yun Cao Jing-Ping Yun Dan Xie Mu-Yan Cai 《PloS one》2014,9(1)
Background
Protein tyrosine phosphatase non-receptor type 12 (PTPN12), has been identified as a potent tumor suppressor in human cancers and a critical regulator of cell adhesion and migration. However, the PTPN12 expression and its prognostic significance in HCC have not been well elucidated.Methodology/Principal Findings
In this study, tissue microarray-based immunohistochemistry (IHC) was investigated in an HCC cohort with adjacent liver tissues as controls. The resulting data were analyzed using receiver operating characteristic curves, Spearman''s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression modeling. Our results showed that decreased expression of PTPN12 was more frequently observed in HCC tissues compared to the adjacent non-tumorous liver tissues. Further correlation analyses indicated that the decreased PTPN12 expression was closely correlated with tumor recurrence (P = 0.015). Univariate analysis showed a significant association between decreased expression of PTPN12 and adverse cancer-specific survival and recurrence-free survival (P<0.001). In different subsets of overall patients, PTPN12 expression was also a prognostic indicator in patients with stage I/II or stage III/IV (P<0.05). Importantly, multivariate analysis (P<0.05) identified PTPN12 expression in HCC as an independent prognostic factor.Conclusions/Significance
Our findings provide a basis for the concept that PTPN12 protein expression is frequently decreased or lost in human HCC tissues and that decreased PTPN12 expression may represent an acquired recurrence phenotype of HCC and that PTPN12 expression may act as a biomarker of prognosis for patients with HCC. 相似文献16.
17.
Fang-Nan Song Meng Duan Long-Zi Liu Zhi-Chao Wang Jie-Yi Shi Liu-Xiao Yang Jian Zhou Jia Fan Qiang Gao Xiao-Ying Wang 《PloS one》2014,9(9)
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. 相似文献18.
Jianxiong Wu Jun Du Liguo Liu Qian Li Weiqi Rong Liming Wang Ying Wang Mengya Zang Zhiyuan Wu Yawei Zhang Chunfeng Qu 《PloS one》2012,7(12)
Background and Aims
Primary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.Methods
A cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.Results
All the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (≥0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34–4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNFα was included.Conclusion
Both tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients. 相似文献19.
Chuan Li Tian-Fu Wen Lu-Nan Yan Bo Li Jia-Ying Yang Ming-Qing Xu Wen-Tao Wang Yong-Gang Wei 《PloS one》2013,8(8)
Aim
The selection criteria for patients with hepatocellular carcinoma (HCC) to undergo liver transplantation should accurately predict posttransplant recurrence while not denying potential beneficiaries. In the present study, we attempted to identify risk factors associated with posttransplant recurrence and to expand the selection criteria.Patients and Methods
Adult patients with HCC who underwent liver transplantation between November 2004 and September 2012 at our centre were recruited into the current study (N = 241). Clinical and pathological data were retrospectively reviewed. Patients who died during the perioperative period or died of non-recurrence causes were excluded from this study (N = 25). All potential risk factors were analysed using uni- and multi-variate analyses.Results
Sixty-one recipients of 216 qualified patients suffered from recurrence. Similar recurrence-free and long-term survival rates were observed between living donor liver transplant recipients (N = 60) and deceased donor liver transplant recipients (N = 156). Total tumour volume (TTV) and preoperative percentage of lymphocytes (L%) were two independent risk factors in the multivariate analysis. We propose a prognostic score model based on these two risk factors. Patients within our criteria achieved a similar recurrence-free survival to patients within the Milan criteria. Seventy-one patients who were beyond the Milan criteria but within our criteria also had comparable survival to patients within the Milan criteria.Conclusions
TTV and L% are two risk factors that contribute to posttransplant recurrence. Selection criteria based on these two factors, which are proposed by our study, expanded the Milan criteria without increasing the risk of posttransplant recurrence. 相似文献20.
Yong-Sheng Xiao Qiang Gao Xiang-Nan Xu Yi-Wei Li Min-Jie Ju Ming-Yan Cai Chen-Xin Dai Jie Hu Shuang-Jian Qiu Jian Zhou Jia Fan 《PloS one》2013,8(8)