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PDF file - 114KB, Supplementary Figure 4. Suppression of MAPK/ERK signaling by SYK(L), but not SYK(S), in HCC cell lines and xenografts.

PDF file - 72KB, Supplementary Table 1. PCR primers and Sources.

PDF file - 127KB, Supplementary Table 3. Cox multivariate analysis of contributory factors to TTR and OS among 152 HCC patients after hepatectomy.

PDF file - 122KB, Supplementary Figure 1. (A) Domain structure of SYK(L) and SYK(S). Sequence and cross-species homology of 23 amino acid residues deleted in SYK(S) are shown. (B) Relative position of PCR primers unique for SYK(L) or SYK(S).

PDF file - 154KB, Supplementary Figure 2. Differential subcellular distribution of SYK(L) and SYK(S) in HCC.

PDF file - 83KB, Supplementary Table 2. Univariate prognostic analyses of recurrence and OS rates for 152 HCC patients after hepatectomy.

PDF file - 192KB

The spleen tyrosine kinase (SYK) has been reported as a novel biomarker for human hepatocellular carcinoma, but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in hepatocellular carcinoma. SYK(L) was downregulated in 38% of human specimens of hepatocellular carcinoma examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis. SYK(S) expression correlated with pathologic parameters characteristic of tumor metastasis, including multiple tumors (P = 0.003) and vascular invasion (P = 0.001). Further, SYK(S) was specifically associated with epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma specimens. Functional studies showed that SYK(S) promoted tumor growth, suppressed apoptosis, and induced EMT through the extracellular signal–regulated kinase pathway, countering the opposite effects of SYK(L). Patients with SYK(L+/S−) tumors exhibited longer overall survival and time to recurrence than those with SYK(L−/S−) or SYK(L+/S+) tumors (P < 0.001). Taken together, our findings showed that SYK(S) enhances invasion, whereas SYK(L) inhibits metastasis in hepatocellular carcinoma. We suggest that SYK(L) downregulation or SYK(S) elevation are strong predictors of poor survival in patients with hepatocellular carcinoma, indicative of a need for aggressive therapeutic intervention. Cancer Res; 74(6); 1845–56. ©2014 AACR.

PDF file - 166KB, Supplementary Figure 3. Effects of suppressed expression of SYK(L) or SYK(S) on cell proliferation and invasion in Huh7 SYK(L)-positive (A), MHCC-97H both SYK(L) and SYK(S)-positive (B), and SMMC7721 cells ectopically expressing SYK(L) (C) or SYK(S) (D).

Background and Aims: Whether surgical resection or repeated ablation should be recommended for intrahepatic recurrent hepatocellular carcinoma (HCC) conforming to the Milan criteria after initial ablation remains unclear. In this study, we compared the outcomes of patients who underwent surgical resection with those who underwent re-ablation for recurrent HCC after initial curative-intent ablation. Methods: The data of 28 and 98 patients who underwent surgical resection and re-ablation, respectively, for recurrent HCC after initial ablation between January 2003 and 2017 were analyzed using propensity score matching. Results: Before matching, the 1-, 3-, and 5-year overall survival (OS) rates were 95.7, 83.0, and 74.4% for the ablation group, compared to 92.9, 89.1, and 70.9% for the resection group (p = 0.490). The corresponding disease-free survival (DFS) rates were 67.5, 40.1, and 25.6% for the ablation group and were 85.4, 59.9, and 53.3% for the resection group (p = 0.018). After matching, the 1-, 3-, and 5-year OS rates for the ablation and resection group were 95.2, 85.5 and 81.8% versus 96.0, 96.0, and 76.4%, respectively (p = 0.550). The 1-, 3-, and 5-year DFS rates were 58.0, 39.5, and 29.9% for the ablation group and were 95.8, 67.2, and 59.8% for the resection group (p = 0.004). Cox proportional hazards model identified surgical resection as the only significant prognostic factor for DFS but not for OS. Conclusion: For intrahepatic recurrent HCC patients after initial ablation, surgical resection could provide better DFS than re-ablation, while no difference in OS was observed between the 2 treatment groups.

Angiogenesis, one of the hallmarks of cancer, is essential for both tumor growth and metastasis. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are largely unknown. Here, we report the role of HOXA5 in tumor angiogenesis of HCC. Methods: The expression of miR-130b-3p and HOXA5 was determined by qRT-PCR and immunohistochemistry, respectively. Capillary tube formation assay, chicken chorioallantoic membrane assay, and subcutaneous xenograft experiments were performed to investigate the role of miR-130-3p and HOXA5. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to evaluate the interaction between Sp1, miR-130b-3p and HOXA5. Results: miR-130b-3p was found up-regulated in HCC and correlated with a poor prognosis. miR-130b-3p promoted HCC angiogenesis both in vitro and in vivo. Mechanistically, HOXA5 was validated as a direct target of miR-130b-3p. Furthermore, we demonstrated that HOXA5 was down-regulated in HCC and its down-regulation was associated with larger tumor size, shorter overall survival, and higher recurrence probability. Moreover, HOXA5 was significantly associated with angiogenesis biomarkers such as CD31 and CD34. Functional studies revealed that the knockdown of HOXA5 also significantly promoted HCC angiogenesis both in vitro and in vivo. Knocking-down HOXA5 significantly provoked HCC cells to induce the capillary tube formation, migration and proliferation of endothelial cells. In xenograft animal models, we found that a decrease of HOXA5 effectively enhanced tumor growth and increased microvessel densities. We further demonstrated that miR-130b-3p could be directly transcriptionally regulated by Sp1. Conclusions: This study showed that a dysregulation in the Sp1/miR-130b-3p/HOXA5 axis contributed to HCC progression and angiogenesis, and that HOXA5 can be considered as a promising therapeutic target for treating HCC.

BACKGROUND & AIMS Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy). METHODS A total of 580 patients with ErHCC were enrolled retrospectively. The association between the independent baseline and the time-dependent variables and PRS was evaluated by cox regression. The prediction accuracy of the inflammation-based prognostic scores was assessed by time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses. RESULTS The GPS, mGPS, PI, PNI, NLR, PLR, LMR and SII were all related to the PRS of ErHCC patients, while only the SII (P

Two-pore-domain (KCNK, K2P) K+ channels are transmembrane protein complexes that control the flow of ions across biofilms, which underlie many essential cellular functions. Because KCNK family members are known to contribute to tumorigenesis in various types of cancer, we hypothesized that they might be differentially expressed in hepatocellular carcinoma (HCC) cells as compared to healthy tissue and serve as diagnostic or prognostic biomarkers. We tested this hypothesis through bioinformatic analyses of publicly available data for the expression of various KCNK subunits in HCC. We observed reduced expression of KCNK2, KCNK15, and KCNK17 in liver cancer, as well as overexpression of KCNK9, all of which correlated with a better prognosis for HCC patients per survival analyses. Moreover, ROC curves indicated that KCNK2, KCNK9, KCNK15, and KCNK17 levels could be used as a diagnostic biomarker for HCC. Finally, our western blot and qRT-PCR results were consistent with those obtained from bioinformatic analyses. Taken together, these results suggest that KCNK2, KCNK9, KCNK15, and KCNK17 could serve as potential diagnostic and prognostic biomarkers of HCC.

The recurrence after curative hepatectomy is common. Limited data have investigated the effect of transcatheter arterial chemoembolization (TACE) combined with ablation in treating recurrent intermediate-stage hepatocellular carcinoma (HCC) after hepatectomy. We aim to compare the efficacy of TACE combined with ablation versus TACE alone in treating recurrent intermediate-stage HCC after hepatectomy. A total of 183 patients with recurrent intermediate-stage HCC after hepatectomy were enrolled at Sun Yat-sen University Cancer Centre, including 111 patients who underwent TACE alone and 72 patients who underwent TACE combined with ablation (TACE–Ablation). Overall survival (OS) and progression-free survival (PFS) were compared by the log-rank test. Propensity score matching (PSM) was used to reduce the confounding bias. Before PSM, the 5-year OS rates were 43.3% vs. 27.9% (P = 0.001), and the 5-year PFS rates were 21.7% vs. 13.0% (P

Background: Whether the efficient heat-generating mechanism of microwave ablation (MWA) is comparable with resection (RES) in treating hepatocellular carcinoma (HCC) remains unclear. Methods: This retrospective cohort study comprised 126 and 1183 patients with HCC meeting the Milan criteria who received MWA or RES between 2002 and 2017. We compared 5-year overall survival (OS) and recurrence-free survival (RFS) using both propensity-score matching (PSM) and inverse-probability-of-treatment-weighting (IPW) analysis and investigated the prognostic factors with multivariate Cox analysis. Results: After PSM (1:2), although MWA ( n = 116) offered decreased 5-year RFS (30.6% versus 57.5%, p 3.0 cm, or multifocal HCCs within the Milan criteria, patients with liver function of albumin–bilirubin grade 1 or 2, and older (⩾60 years) or younger (Conclusions: Compared with RES, MWA offered worse RFS for HCC within the Milan criteria; however, both treatments provided equivalent long-term OS because most patients with intrahepatic recurrence remained eligible for repeat treatments.

Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.e., those with portal vein tumor thrombosis, adjacent organ involvement or tumor rupture) who underwent resection were analyzed. The patients were categorized into the sorafenib group (n=14) or the best supportive care (BSC) group (n=28). Although the histological grade, Barcelona Clinic Liver Cancer Stage, tumor size, nodule number and proportion of patients with high serum α-fetoprotein levels were comparable between the sorafenib and BSC groups, those receiving sorafenib following resection had significantly longer disease-free survival (DFS) of 5.2 months [95% confidence interval (CI), 1.2-9.2 months] compared with the BSC group [1.8 months (95% CI, 0.6-3.0 months)]. No differences in overall survival were noted between the groups. Furthermore, no drug-related adverse events resulted in discontinuation of sorafenib therapy. Univariate log-rank analysis revealed that sorafenib treatment (P=0.002) and treatment prior to resection (P=0.012) were significantly associated with longer DFS; however, sorafenib therapy (P=0.027) and tumor size (P=0.028) were associated with longer DFS by multivariate analysis. Furthermore, sorafenib was well-tolerated and improved DFS in patients with advanced HCC who underwent hepatic resection. Thus, tumor resection followed by sorafenib therapy may represent an effective therapeutic strategy for patients with advanced HCC. This possibility should be confirmed in larger, multicenter studies.

Background Apatinib, a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR 2), has exhibited modest antitumor efficacy in hepatocellular carcinoma (HCC). We aimed to evaluate the effectiveness and tolerability of apatinib versus sorafenib in patients with advanced HCC. Methods All patients with advanced HCC who underwent sorafenib or apatinib between January 2016 to December 2017 were retrospectively reviewed. Seventy-two patients received apatinib (26 patients, 500 mg, daily) or sorafenib (46 patients, 400 mg, twice daily) until disease progression or intolerable toxicities. Primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (RECIST), disease control rate (DCR), and safety. Results The median follow-up was 13.2 (5.7-20.7) months. The 1-year OS for apatinib of 62.0% was comparable to that of sorafenib [64.2%, hazard ratio (HR), 1.15; 95% confidence interval (CI), 0.369-3.58]. The median PFS was 4.1 months in the apatinib group (95% CI, 3.2 to 7.4 months) and 3.6 months in the sorafenib group (95% CI, 2.7 to 5.9 months; HR, 1.03; 95% CI, 0.586 to 1.800; P=0.925). The apatinib group exhibited higher ORR (19.2% vs. 2.2%, P=0.012) but similar DCR (57.7% vs. 50%, P=0.530) compared with the sorafenib group. The most common any-grade adverse events in the apatinib and sorafenib groups were hand and foot syndrome (53.8% vs. 50%), hypertension (50% vs. 19.6%), diarrhea (34.6% vs. 28.3%), and elevated transaminase (57.7% vs. 63%). Conclusions Compared with sorafenib, apatinib yielded comparable PFS and OS, and even better ORR, in patients with advanced HCC.

Supplemental material, Supplementary_figure_legends for Microwave ablation versus resection for hepatocellular carcinoma within the Milan criteria: a propensity-score analysis by Wenwu Liu, Ruhai Zou, Chenwei Wang, Jiliang Qiu, Jingxian Shen, Yadi Liao, Zhiwen Yang, Yuanping Zhang, Yongjin Wang, Yichuan Yuan, Kai Li, Dinglan Zuo, Wei He, Yun Zheng, Binkui Li and Yunfei Yuan in Therapeutic Advances in Medical Oncology

To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE). We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE. Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p

With development of surgical technology, we aimed to investigate whether resection could challenge the standard treatment, ablation, in treating multifocal hepatocellular carcinomas meeting the Barcelona-Clinic Liver Cancer A stage. From January 2005 to January 2017, the oncological outcomes of patients undergoing resection (n = 72) or ablation (n = 63) were retrospectively analysed using propensity score matching. At baseline, patients in the ablation group had more tri-focal lesions (30.2% vs. 6.9%, P = 0.001) and smaller tumours (2.00 cm vs. 2.50 cm, P = 0.002) than resection group. After matching, the baseline was well-balanced between treatments (n = 46 pairs); resection provided comparable 5-year overall survival (77.0% vs. 83.6, P = 0.790) and superior 5-year recurrence-free survival (40.4% vs. 16.9%, P = 0.022) to ablation. The multivariate Cox model confirmed that ablation was not associated with worse overall survival (HR = 0.89; 95% CI, 0.33 - 2.42, P = 0.819), but identified ablation as an unfavourable predictor of recurrence-free survival (HR = 2.13; 95% CI, 1.27 - 3.57, P

Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, hepatitis B virus (HBV)-infected, hepatitis C virus (HCV)-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively). A polymerase chain reaction (PCR) array was used to detect the changes in transcription factor (TF) expression in hepatic stellate cells (HSCs) with SYK knockdown. The effects of SYK antagonism on liver fibrogenesis were studied in LX-2 cells, TWNT-4 cells, primary human HSCs, and three progressive fibrosis/cirrhosis animal models, including a CCL4 mouse model, and diethylnitrosamine (DEN) and bile duct ligation (BDL) rat models. We found that SYK protein in HSCs and hepatocytes correlated positively with liver fibrosis stage in human liver tissue. HBV or HCV infection significantly increased SYK and cytokine expression in hepatocytes. Increasing cytokine production further induced SYK expression and fibrosis-related gene transcription in HSCs. Up-regulated SYK in HSCs promoted HSC activation by increasing the expression of specific TFs related to activation of HSCs. SYK antagonism effectively suppressed liver fibrosis via inhibition of HSC activation, and decreased obstructive jaundice and reduced HCC development in animal models. Conclusion: SYK promotes liver fibrosis via activation of HSCs and is an attractive potential therapeutic target for liver fibrosis and prevention of HCC development. (Hepatology 2018).

Objective: The present study aimed to investigate the effectiveness of parenteral nutritional support with ω-3 PUFAs–based lipid emulsions in patients after liver resection. Methods: A total of 119 patients were randomly assigned to the immunonutrition (IM) group (n = 59) and control group (n = 60). The IM group was continuously given Omegaven® 10% 100 mL/day rather than regular nutrition for five days postoperatively. Venous blood samples were obtained from all subjects before surgery and D1, D3 and D7 after surgery. Results: No significant difference was found in baseline characteristics of the two groups. On D1 after surgery, no statistically significant differences were observed in the blood sample tests between the two groups. On D3 after surgery, the levels of white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) were dramatically decreased in the IM group (t = 3.065, p = 0.003; t = 2.149, p = 0.034; t = 5.313, p= 0.001; and t = 2.419, p = 0.017, respectively). Furthermore, on D7 after surgery, not only could a significant decrease be observed in the IM group concerning the levels of WBC, ALT and TBil (t = 3.025, p = 0.003; t = 2.094, p = 0.038; and t = 2.046, p = 0.043, respectively), but it was also seen in the level of Δprothrombintime (PT) (t = 2.450, p = 0.016). An increase in the level of prealbumin (Pre-Alb) in the IM group was observed on D7 after surgery (t = 2.237, p = 0.027). The frequency of total complications in the IM group were significantly lower than in the control group (χ2 = 4.225, p = 0.040 and χ2 = 3.174, p = 0.075). The trend favored the IM group in reducing the total infective complications rate (χ2 = 3.174, p = 0.075). A significant decrease in the duration of the hospital stay after surgery was also observed in the IM group (t = 2.012, p = 0.047).Conclusion: ω-3 PUFAs–based lipid emulsions for treatment of patients after hepatectomy are safe and effective in controlling inflammation, protecting liver function, and consequently reducing the rate of total complications and the duration of the hospital stay.

Background Whether portal hypertension (PHT) is an appropriate contraindication for hepatic resection (HR) in hepatocellular carcinoma (HCC) patient is still under debate. Aims: Our aim was to assess the impact of clinically significant PHT on postoperative complication and prognosis in HCC patients who undergo HR. Methods Two hundred and nine HCC patients who underwent HR as the initial treatment were divided into two groups according to the presence (n = 102) or absence (n = 107) of clinically significant PHT. Propensity score matching (PSM) analysis was used to compare postoperative outcomes and survival. Results Before PSM, PHT patients had higher rates of postoperative complication (43.1% vs. 23.4%; P = 0.002) and liver decompensation (37.3% vs. 17.8%; P = 0.002) with similar rates of recurrence-free survival (RFS; P = 0.369) and overall survival (OS; P = 0.205) compared with that of non-PHT patients. However, repeat analysis following PSM revealed similar rates of postoperative complication (32.2% vs. 39.0%; P = 0.442), liver decompensation (25.4% vs. 32.2%; P = 0.416), RFS (P = 0.481) and OS (P = 0.417; 59 patients in each group). Presence of PHT was not associated with complication by logistic regression analysis, or with overall survival by Cox regression analysis. Conclusions The presence of clinically significant PHT had no impact on postoperative complication and prognosis, and should not be regarded as a contraindication for HR in HCC patients.

Goals and background The role of preventive lymphadenectomy has not yet been determined for hepatocellular carcinoma (HCC) patients. We designed a study to evaluate the effect of hepatectomy combined with preventive lymphadenectomy on HCC patients. Study Patients were randomly divided into group A (treated with hepatectomy alone) and group B (underwent hepatectomy combined with lymphadenectomy). The postoperative complications and oncologic prognoses were analyzed. Results Of the 85 patients enrolled into this study, 79 cases (38 in group A and 41 in group B) were pathologically confirmed to have HCC and received curative resection. One hundred and sixteen lymph nodes were dissected and evaluated as negative by the pathologist. The 12-, 36-, and 60-month disease-free survival rates of group A were 81.6%, 68.4%, and 63.2%, respectively, whereas they were 78.0%, 65.9%, and 63.4%, respectively, for group B. The 12-, 36-, and 60-month overall survival rates in group A were 94.7%, 78.9%, and 65.8%, respectively, whereas they were 87.8%, 78.0%, and 70.7%, respectively, in group B. The differences in the disease-free survival and overall survival between the 2 groups were not statistically significant according to the log-rank test (P=0.811 and P=0.881, respectively). The difference in the surgical complication rate between groups A and B was not statistically significant (47.4% vs. 36.6%, P=0.332). Conclusions Although hepatectomy combined with regional lymphadenectomy is a safe procedure, preventive lymphadenectomy may not decrease the rate of tumor recurrence nor improve the prognosis in early-stage HCC patients.

Objective: To investigate the association between serum concentration of insulin-like growth factor (IGF) and the risk of pancreatic cancer (PaC). Methods: We identified eligible studies in Medline and EMBASE databases (no reference trials from 2014 to 2016) in addition to the reference lists of original studies and review articles on this topic. A summary of relative risks with 95% confidence intervals (CI) was calculated using a random-effects model. The heterogeneity between studies was assessed using Cochran Q and I2 statistics. Results: Ten studies (seven nested case-control studies and three retrospective case-control studies) were selected as they met our inclusion criteria in this meta-analysis. All these studies were published between 1997 and 2013. The current data suggested that serum concentrations of IGF-I, IGF-II and insulin-like growth factor binding protein-3 (IGFBP-3)in addition to the IGF-I/IGFBP-3 ratio were not associated with an increased risk of PaC (Summary relative risks (SRRs) = 0.92, 95% CI: 0.67–1.16 for IGF-I; SRRs = 0.84, 95% CI: 0.54–1.15 for IGF-II; SRRs = 0.93, 95% CI: 0.69–1.17 for IGFBP-3; SRRs = 0.97, 95% CI: 0.71–1.23 for IGF-I/IGFBP-3 ratio). There was no publication bias in the present meta-analysis. Conclusion: Serum concentrations of IGF-I, IGF-II, IGFBP-1 and IGFBP-3 as well as the IGF-I/IGFBP-3 ratio were not associated with increased risk of PaC.

With recent improvements in operative techniques, many studies have reported that resection is safe for hepatocellular carcinoma (HCC) patients with portal hypertension (PHT). However, no direct evidence exists to compare resection with ablation in patients with hepatitis B virus (HBV)-related PHT.Of 259 HBV-related PHT patients who met the Milan criteria, 123 patients underwent resection and 136 underwent ablation as a primary treatment. Complications were graded with the Clavien-Dindo system, and oncologic outcomes were analyzed with a propensity score matching (PSM) method.Compared with the ablation group, the resection group showed larger tumors, greater white blood cell counts, greater platelet counts, lower γ-glutamyltransferase levels, and lower model of end stage liver disease scores (all P.05). Although more frequent complications occurred in the resection group (P.001), the difference was significant for the Grade I complications but not for Grade II-V complications. The recurrence-free survival (RFS) and overall survival (OS) rates were greater in the resection group than in the ablation group (P = .001 and P = .010, respectively). After one-to-one PSM, 77 resection patients and 77 ablation patients were selected for further analyses. The advantages of resection over ablation were still observed in RFS (P = .002) and OS (P = .012). Grade I-V complications were comparable between the 2 groups (all P.100).Resection is safe and confers a survival advantage over ablation in HBV-related PHT patients. Resection may be recommended as an optimal treatment for these patients.

MicroRNA-130a (miR-130a) has recently been found to be implicated in many critical processes in various types of human cancer. However, the prognostic value of miR-130a in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the expression of miR-130a in HCC and analyzed its association with clinical features and prognosis of HCC patients. We determined the expression level of miR-130a in 102 cases of paired HCC and adjacent non-tumor tissues by quantitative real-time PCR (qRT-PCR). The qRT-PCR results showed that the miR-130a expression was significantly down-regulated in tumor tissues compared with the adjacent non-tumor tissues (P

The spleen tyrosine kinase (SYK) has been reported as a novel biomarker for human hepatocellular carcinoma, but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in hepatocellular carcinoma. SYK(L) was downregulated in 38% of human specimens of hepatocellular carcinoma examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis. SYK(S) expression correlated with pathologic parameters characteristic of tumor metastasis, including multiple tumors (P = 0.003) and vascular invasion (P = 0.001). Further, SYK(S) was specifically associated with epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma specimens. Functional studies showed that SYK(S) promoted tumor growth, suppressed apoptosis, and induced EMT through the extracellular signal–regulated kinase pathway, countering the opposite effects of SYK(L). Patients with SYK(L+/S−) tumors exhibited longer overall survival and time to recurrence than those with SYK(L−/S−) or SYK(L+/S+) tumors (P < 0.001). Taken together, our findings showed that SYK(S) enhances invasion, whereas SYK(L) inhibits metastasis in hepatocellular carcinoma. We suggest that SYK(L) downregulation or SYK(S) elevation are strong predictors of poor survival in patients with hepatocellular carcinoma, indicative of a need for aggressive therapeutic intervention. Cancer Res; 74(6); 1845–56. ©2014 AACR.