Jiliang Qiu

Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma

BackgroundMetastasis-associated in colon cancer-1 (MACC1) is a newly identified gene that plays a role in colon cancer metastasis through upregulation of c-MET proto-oncogene (c-MET). However, the value of MACC1 as a potential biomarker for hepatocellular carcinoma (HCC) remains unknown.MethodsMACC1 mRNA expression in 128 HCC tissues was examined by quantitative polymerase chain reaction. To show the potential correlation of MACC1 and c-MET, c-MET was also analysed.ResultsMACC1 was more highly expressed in HCC than in non-HCC tissues (P = 0.009). High MACC1 expression was significantly increased in cases with high alpha fetoprotein (AFP) (P = 0.025). A positive correlation was found between MACC1 and c-MET mRNAs (r = 0.235, P = 0.009). Both univariate and multivariate analyses revealed that MACC1 expression was associated with overall survival (OS) and disease-free survival (DFS). Moreover, stratified analysis showed that tumour-node-metastasis (TNM) stage I patients with high MACC1 levels had shorter OS and DFS than those with low MACC1.ConclusionsMACC1 may identify low- and high-risk individuals with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I patients. MACC1 may serve as a novel biomarker for HCC.

Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy

OBJECTIVES The present study was aimed to explore the prognostic strength of Sox2 and Oct4A in hepatocellular carcinoma (HCC). DESIGN AND METHODS We investigated the expression of Sox2 and Oct4A in five hepatoma cell lines, one immortalized normal liver cell line, HCC tissues with matched nontumorous liver tissues and normal liver tissues by reverse transcription-polymerase chain reaction. RESULTS Sox2 and Oct4A mRNA were overexpressed in hepatoma cell lines and tumor tissues. Sox2 or Oct4A positive expression was significantly associated with an aggressive phenotype. Both univariate and multivariate analyses revealed that Sox2 or Oct4A was an independent prognostic factor for HCC. When using subgroup analysis, the patients with a co-expression of Sox2/Oct4A had the poorest prognosis. Further analysis demonstrated that Sox2 alone or Sox2/Oct4A could stratify outcome in HCC patients with early stage. CONCLUSIONS Sox2 and Oct4A can be novel predictors of poor prognosis for patients undergoing resection of HCC.

CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular Carcinoma: Results From a Multicenter Study

Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip. Two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to select significant CpGs. In the training phase, penalized Cox regression was used to further narrow CpGs into 140 samples. In the validation phase, candidate CpGs were validated using an internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector Operation and the Support Vector Machine-Recursive Feature Elimination algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase inhibitor 3 were highlighted as candidate predictors in the training phase. On the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was developed to classify patients into high- and low-risk recurrence groups in the training cohort ( P < .001). The performance of MSEH was validated in the internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, hepatitis B virus surface antigen, and antivirus therapy was generated to predict the 5-year recurrence-free survival in the training cohort, and it performed well in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, respectively). Conclusion MSEH, a three-CpG-based signature, is useful in predicting recurrence for patients with E-HCC.

Expression and prognostic significance of CIP2A mRNA in hepatocellular carcinoma and nontumoral liver tissues

Objective: This study was undertaken to determine the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in predicting prognosis of hepatocellular carcinoma (HCC). Methods: CIP2A mRNA level of 136 pairs of tumor and nontumoral liver tissues of HCC patients after hepatectomy were investigated by quantitative real-time reverse transcription polymerase chain reaction. Results: Intratumoral CIP2A mRNA was not associated with patients’ prognosis. However, nontumoral CIP2A mRNA, which was correlated with lack of tumor encapsulation, poor tumor differentiation, intrahepatic metastasis, and high tumor-node-metastasis stage was an independent risk factor for overall survival and recurrence-free survival. Conclusions: Nontumoral CIP2A mRNA expression might serve as a novel biomarker for HCC patients undergoing resection.

The role of clinically significant portal hypertension in hepatic resection for hepatocellular carcinoma patients: a propensity score matching analysis.

BackgroundWhether 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.MethodsTwo 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.ResultsBefore 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.ConclusionsThe 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.

Clinical features and outcome of multiple primary malignancies involving hepatocellular carcinoma: A long-term follow-up study

BackgroundThe prolonged survival of individuals diagnosed with cancer has led to an increase in the number of secondary primary malignancies. We undertook to perform a definitive study to characterize and predict prognosis of multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC), due to the scarcity of such reports.MethodsClinicopathological data were analyzed for 68 MPM patients involving HCC, with 35 (target group) underwent curative liver resection. Additional 140 HCC-alone patients with hepatectomy were selected randomly during the same period as the control group.ResultsOf the 68 patients with extrahepatic primary malignancies (EHPM), 22 were diagnosed synchronously with HCC, and 46 metachronously. The most frequent EHPM was nasophargeal carcinoma, followed by colorectal and lung cancer. Univariate analysis demonstrated that synchronous (P = 0.008) and non-radical treatment for EHPM (P < 0.001) were significant risk factors associated with poorer overall survival (OS). While, Cox modeling revealed that the treatment modality for EHPM, but not the synchronous/metachronous determinant, was an independent factor for OS, and that therapeutic option for HCC was an independent factor for HCC-specific OS. Moreover, no HCC-specific overall and recurrence-free survival benefit were observed in the control group when compared with that of the target group (P = 0.607, P = 0.131, respectively).ConclusionsCurative treatment is an independent predictive factor for OS and HCC-specific OS, and should been taken into account both for synchronous and metachronous patients. MPM patients involving HCC should not be excluded from radical resection for HCC.

Resection versus ablation in hepatitis B virus-related hepatocellular carcinoma patients with portal hypertension: A propensity score matching study.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Hepatectomy for hepatocellular carcinoma patients with macronodular cirrhosis

Objective Patients with hepatocellular carcinoma (HCC) presenting with nonmicronodular or micronodular cirrhosis are usually treated by hepatectomy. The value of resection for patients with hepatitis B virus-related macronodular cirrhosis, however, remains unknown because of potentially fatal complications of this procedure. Methods Clinicopathological data were analyzed for 85 resected HCC patients with hepatitis B virus-related macronodular cirrhosis. An additional 255 patients with nonmicronodular and micronodular cirrhosis were randomly selected during the same period as the control group. Results Compared with nonmicronodular and micronodular cirrhosis patients, macronodular cirrhotic patients exhibited elevated alanine aminotransferase, aspartate aminotransferase, and &ggr;-glutamyltransferase levels, higher Child–Pugh classification, higher indocyanine green retention rate at 15 min (ICG R15), and more number of total complications. No significant differences were observed between the two groups with regard to major complications, mortality, overall survival, and recurrence-free survival. The morbidity rate was relatively low in patients exhibiting low ICG R15 (<10%). Cox analysis identified small tumors (⩽5 cm) and radical resection as independent prognostic factors that could predict long-term overall survival. Radical resection can result in high recurrence-free survival in macronodular cirrhotic patients. Conclusion Resection is safe for macronodular cirrhotic HCC patients, and radical resection provides a positive outcome. Small-sized patients are good candidates for hepatectomy. Macronodular cirrhosis should not rule out hepatectomy in patients with low ICG R15.

Microwave vs radiofrequency ablation for hepatocellular carcinoma within the Milan criteria: a propensity score analysis

Whether microwave ablation (MWA) challenges the standard role of radiofrequency ablation (RFA) in treating early‐stage hepatocellular carcinoma (HCC) remains unclear.

Sorafenib therapy following resection prolongs disease‑free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

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.