Background & aimsHepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is prevalent worldwide. Despite its limitations, serum alpha-fetoprotein (AFP) remains the most widely-used biomarker for the diagnosis of HCC. This study aimed to assess whether measurement of peripheral plasma Dickkopf-1 (DKK1) and Tie2-expressing monocytes (TEMs) could overcome the limitations of AFP and improve the diagnostic accuracy of HCC.MethodsPlasma DKK1 level and the percentage of TEMs in peripheral CD14+CD16+ monocytes from HCC patients (n = 82), HBV-related liver cirrhosis (LC) patients (n = 29), chronic hepatitis B (CHB) infected patients (n = 28) and healthy volunteers (n = 31) were analyzed by ELISA and flow cytometry. Receiver operating characteristic (ROC) curves were used to analyze a single biomarker, or a combination of two or three biomarkers. Univariate and multivariate analyses were performed to assess the significance of each marker in prediction of HCC and AFP-negative HCC from LC patients.ResultsThe percentage of TEMs in peripheral CD14+CD16+ monocytes and plasma level of DKK1 in HCC group were significantly higher than those in LC, CHB and healthy control groups (all P-values <0.05). The percentage of TEMs alone was also significantly higher in AFP-negative HCC group than that in LC, CHB and healthy control groups (all P-values <0.05). Plasma DKK1 level alone could not distinguish between AFP-negative HCC and LC patients. ROC curves showed that the optimal diagnostic cutoff value was 550.93 ng/L for DKK1 and 4.95% for TEMs. There was no significant difference in AUC of DKK1, TEMs and AFP in HCC diagnosis between the four groups (all P>0.05). A combination of DKK1, TEMs and AFP measurements increased the AUC for HCC diagnosis as compared with either marker alone (0.833; 95%CI 0.768–0.886). The AUC for TEMs was 0.692 (95% CI 0.564–0.819) in differentiating AFP-negative HCC from LC, with a sensitivity of 80.0% and a specificity of 65.52%. Only TEMs prevailed as a significant predictor for AFP-negative HCC differentiating from LC patients in univariate and multivariate analyses (P = 0.016, P = 0.023).ConclusionsTEMs and DKK1 may prove to be potential complementary biomarkers for AFP in the diagnosis of HCC. TEMs rather than DKK1 could serve as a complementary biomarker for AFP in the differential diagnosis of AFP-negative HCC versus LC patients.

Abstract. The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21.0 software. UBE2A mRNA and protein were highly expressed in HCC tissues compared with those in the adjacent normal tissue. Immunohistochemical analysis revealed that UBE2A protein was more strongly stained in the 276 paraffin-embedded HCC tissues as compared with the 63 adjacent normal tissue. Statistical analysis also demonstrated that UBE2A expression was significantly associated with histological differentiation, TNM stage and vascular invasion of HCC (P<0.05). Notably, HCC patients with a high expression of UBE2A had a shorter survival time as compared with those with a low expression of UBE2A. There results suggested that UBE2A may be involved in the pathogenesis of HCC and may serve as an important prognostic marker.Further exploration of the involvement of UBE2A in HCC development may provide novel therapeutic targets. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide and the fifth most common cancer type (1). HCC is a global health burden and its prevalence varies worldwide (2). The incidence rate is reported to be higher in Asia (>20 cases/100,000 individuals) in comparison with that in North America and Europe (<5 cases/100,000 individuals) (3). The prognosis of HCC is poor, as evident by the fact that the number of annual mortality cases (~600,000) is almost equal to the number of new cases diagnosed annually (4). The median rate for 1-year survival is 80% (range, 63-97%), for 3-year survival is 70% (range, 34-78%) and for 5-year survival is 50% (range, 17-69%) (5). Surgery remains the most important treatment strategy for patients with HCC. The 5-year survival rate of patients with early HCC subsequent to resection treatment reaches 50%, although these patients exhibit a high recurrence rate (6,7). Despite advances in the diagnosis (8) and treatment (9) of HCC, the prognosis of this disease remains poor (10). Therefore, further clarification of the mechanisms underlying its development is important (11,12).At present, the prognosis of HCC is predicted based on imaging findings and biomarkers. Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited. Consequently, there is an urgency to develop a novel biomarker for the prognosis of HCC.The ubiquitin system serves a ...

e16176 Background: The earlier randomized phase III RESORCE trial and several real-world studies demonstrate that regorafenib improves overall survival (OS) in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of regorafenib alone or in combinations in advanced HCC. Methods: 60 Patients with pathologically or clinically diagnosed advanced HCC were enrolled. We retrospectively analyzed the efficacy and safety of patients who received at least one cycle of regorafenib between March 7, 2019 and December 25, 2022 in the Affiliated Hospital of Nantong University and Nantong Third People's Hospital. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). The secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. The safety and efficacy were assessed by investigators per CTCAE v5.0 and mRECIST v1.1, respectively. Data on survival rates were calculated using the Kaplan-Meier method. Results: The average age was 62.63 years, and 95% were male. Most patients had a Child-Pugh A score (73.3%), and the proportion of patients with BCLC stage B and C classes were 41.7% and 58.3%, respectively. 3 (5%) patients received single-drug regorafenib therapy, and the remaining patients (95%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (10%), regorafenib combined with TACE (40%), and triple therapy (TKI, ICI, TACE) (45%). The ORR and DCR were 40% and 92%, respectively. With a median follow-up of 16.10 months (95%CI, 11.067-21.133), the median PFS was 8.4 months (95% CI, 5.597-11.203), and the median OS has not been reached. Most patients tolerated 120mg or 160mg once daily during weeks 1–3 of each 4-week cycle. 23 patients (38.33%) experienced adverse events (AEs). The most frequent AE (≥5%) included hand-foot syndrome (23.33%), diarrhea (11.67%), and fatigue (6.77%). The incidence of grade 3 AE was 3%. No grade 4 AE and new safety signals were identified. Conclusions: Regorafenib alone or in combination had a manageable safety profile and promising efficacy in advanced HCC patients.