Meng-Xin Tian

High expression of 5-hydroxymethylcytosine and isocitrate dehydrogenase 2 is associated with favorable prognosis after curative resection of hepatocellular carcinoma

BackgroundThe expression of 5-hydroxymethylcytosine (5-hmC) and isocitrate dehydrogenase 2 (IDH2) is frequently downregulated in numerous cancers. 5-hmC and IDH2 expression in hepatocellular carcinoma (HCC) has yet to be determined.MethodsThe immunohistochemical expression of 5-hmC and IDH2 were analyzed in tissue microarrays containing samples from 646 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of 5-hmC and IDH2 were evaluated by Cox regression and Kaplan-Meier analyses.ResultsWe discovered that low 5-hmC and IDH2 expression was associated with malignant behaviors. Low 5-hmC or IDH2 expression alone and combined 5-hmC and IDH2 expression were associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that 5-hmC or IDH2 and 5-hmC/IDH2 were independent prognostic indicators for OS and time to recurrence (TTR), which was confirmed in an independent validation cohort.Conclusions5-hmC and IDH2 correlate with less aggressive tumor behavior in HCC. When 5-hmC and IDH2 are considered together, they serve as a prognostic marker in patients with surgically resected HCCs.

CCL24 contributes to HCC malignancy via RhoB- VEGFA-VEGFR2 angiogenesis pathway and indicates poor prognosis

CCL24 is one chemotactic factor extensively studied in airway inflammation and colorectal cancer but less studied in hepatocellular carcinoma (HCC) retrospectively. So HCC tissue microarray (TMA) was used to estimate relationship between CCL24 and prognosis, cell experiments were conducted to study its influence for HCC cell biological behavior. CCL24 was injected to nude mice to monitor tumor formation and pulmonary metastasis; qRT-PCR, western blot and Immunohistochemistry were used to explore potential mechanism. CCL24 plays roles in target cells via its downstream CCR3, or it is regulated by Type 2 helper T cells (Th2 cell) factors, so immune related experiments were conducted. Meanwhile, Rho GTPase family have close relation not only with T cell priming, but with neovascularization; CCL24 contributes to neovascularization in age-related macular degeneration via CCR3, so Rho GTPase family, Th2 cell factors, Human Umbilical Vein Endothelial Cells were used to uncover their trafficking. Ultimate validation was confirmed by small interfering RNA. Results showed CCL24 expression was higher in caner tissues than adjacent normal tissues, it could contribute to proliferation, migration, and invasion in HCCs, could accelerate pulmonary metastasis, promote HUVECs tube formation. Th2 cell factors were irrelevant with CCL24 in HCCs; and RhoB, VEGFA, and VEGFR2 correlated with CCL24 in both mRNA and protein level. Downstream RhoB-VEGFA signaling pathway was validated by siRhoB and siVEGFA inhibition. In a word, CCL24 contributes to HCC malignancy via RhoB-VEGFA-VEGFR2 angiogenesis pathway and indicates poor prognosis, which urges us to study further CCL24 effects on diagnosis and potential therapy for HCC.

The SphKs/S1P/S1PR1 axis in immunity and cancer: more ore to be mined

Over the past two decades, huge amounts of research were launched to understand the functions of sphingosine. Many pathways were uncovered that convey the relative functions of biomacromolecules. In this review, we discuss the recent advances of the role of the SphKs/S1P/S1PR1 axis in immunity and cancer. Finally, we investigate the therapeutic potential of new drugs that target S1P signaling in cancer therapy.

Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection

As a rare type of liver cancer, intrahepatic cholangiocarcinoma (ICC) has become an increasingly important malignancy and continues to present significant therapeutic challenges. Since coagulopathy is associated with poor prognosis in hepatocellular carcinoma (HCC), and prognostic factors of ICC after curative resection were still not clear, we aim to analyze the characteristics of ICC patients with coagulopathy and its correlation to prognosis. From January 2000 to June 2011, 541 ICC patients, after curative resection, were enrolled in our study. Survival curves were depicted by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazard regression was adopted for multivariate survival analysis. Students t test was performed to analyze the difference between the coagulopathy group and the normal group. The correlation between coagulation parameters and prognosis was also evaluated. The incidence rate of at least one coagulation parameter abnormality was 22.6% (122/541) while PT was the most common factor (8.87%, 48/541). The one-year survival rate of patients with coagulopathy was significantly lower than that of patients with normal coagulation (p < 0.01). In a univariate analysis, patients with prolonged PT was associated with shortened DFS (p < 0.05). Meanwhile, PT was negatively correlated with pre-albumin level. TNM stage, CA19-9, GGT, and pre-albumin level were independent prognostic factors of DFS in the multivariate analysis. In conclusion, the incidence rate of coagulopathy of ICC patients is lower than HCC patients. Prolonged PT, advanced TNM stage, low pre-albumin level, and high CA19-9 and GGT level were correlated with high recurrence rate and poor prognosis.

A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma

Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

Surgical Treatment of Combined Hepatocellular-Cholangiocarcinoma is as Effective in Elderly Patients as it is in Younger Patients: A Propensity Score Matching Analysis

Aims: To compare the long-term prognosis of younger and elderly patients with combined hepatocellular-cholangiocarcinoma (CHC) who underwent curative resection between 1993 and 2014 at our center. Methods: Two hundred and thirteen patients who underwent liver resection for CHC were enrolled in our study. The overall survival (OS) and disease-free survival (DFS) of elderly patients (age≥60, n=52) and younger patients (age<60, n=161) were compared by multivariate analysis and propensity score matching (PSM) analysis. Results: Among the 213 CHC patients, the elderly patients had a higher rate of worse Child-Pugh grade (P=0.027), abnormal serum albumin (P<0.001) and lymphoid metastases (P=0.024). The proportion of HBV-positive CHC patients (74.6%, 159/213) was much higher than that observed in healthy cohorts. Younger patients had a higher rate of hepatitis B virus (HBV) infection compared to older patients (83.9% vs 46.2%, P<0.001). OS and DFS of the elderly and younger patients before and after propensity score matching were comparable. Conclusion: Elderly and younger patients who underwent liver resection for CHC have comparable long-term OS and DFS.

Cell Death and Autophagy in Liver Tumorigenesis and Liver Cancer

Autophagy, an evolutionarily conserved process, is crucial for survival, development, and homeostasis. It serves to remove damaged cellular components, such as mitochondria and long-lived proteins. Increased understanding of autophagy within liver cancer indicates that, in addition to the role of tumor promotion, autophagy also could suppress cancer progression by various cellular machineries. This chapter summarizes recent advances about dual roles of autophagy in tumor promotion and suppression, and discusses the intrinsic mechanism and application about autophagy inducers and inhibitors in clinical treatments with experimental results developed in vivo and in vitro systems.