Role And Mechanism Of PRMT1 In Hepatocellular Carcinoma(HCC),and Surgical Decision-making For HCC With Portal Vein Tumor Thrombus

Part ? Role and Mechanisms of PRMT1 in Hepatocellular CarcinomaBackground/Aims: Although it has been widely accepted that protein arginine methyltransferase 1(PRMT1)is a cancer-promoting gene in various cancers,the mechanism of PRMT1 in hepatocellular carcinoma(HCC)requires more exploration.This study aimed to investigate the role and mechanisms of PRMT1 in HCC.Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses.Cell proliferation,colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT,crystal violet and Boyden chamber assays.Tumour growth was monitored in a xenograft model,and intrahepatic metastasis models were established.Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and metastasis;PRMT1 expression was also positively correlated with microvascular invasion(P = 0.024),tumour differentiation(P = 0.014),tumour size(P = 0.002),and portal vein tumour thrombus(PVTT)(P = 0.028).Cell proliferation,colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines.Moreover,low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo,as well as tumour metastasis.These phenotypes were associated with STAT3 signalling pathway activation.Cryptotanshinone,a STAT3 inhibitor,inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression.Conclusions: We revealed a signifcant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation.PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.Part ? Surgical Decision-making for Hepatocellular Carcinoma with Portal Vein Tumor ThrombusBackground Portal vein tumour thrombus(PVTT)is a significant poor prognosticfactor for hepatocellular carcinoma(HCC).Patients with PVTT limited to a first-orderbranch of the main portal vein(MPV)or above could benefit from R0 liver resection(LR).An EHBH-PVTT scoring system was established to predict the prognosis of HCC patientswith PVTT after R0 LR,and to guide selection of subgroups of patients that could benefitfrom LR.Methods HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included.The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox-regression model and validated in a prospective internal validation cohort and three external validation cohorts.Results There were 432 patients in the training cohort,285 in the prospective internal validation cohort,and 286,189 and 135 in 3 external validation cohorts,respectively.The score was conducted using total bilirubin,?-fetoprotein,tumour diameter and satellite lesions.The EHBH-PVTT score differentiated two groups of patients(?/>3 points)with distinct long-term prognoses(median OS,17.0 vs 7.9 months;P<0.001).The predictive accuracy,as determined by the area under the time-dependent receiver operating characteristic curves(AUC,0.680 to 0.721),was greater than that of the other commonly used staging systems for HCC and PVTT.Conclusion The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR.It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR.It can be used to supplement the other HCC staging systems.