Background: Predicting early recurrence (ER) after radical therapy for HCC patients is critical for the decision of subsequent follow-up and treatment. Radiomic features derived from the medical imaging show great potential to predict prognosis. Here we aim to develop and validate a radiomics nomogram that could predict ER after curative ablation. Methods: Total 184 HCC patients treated from August 2007 to August 2014 were included in the study and were divided into the training (n = 129) and validation(n = 55) cohorts randomly. The endpoint was recurrence free survival (RFS). A set of 647 radiomics features were extracted from the 3 phases contrast enhanced computed tomography (CECT) images. The minimum redundancy maximum relevance algorithm (MRMRA) was used for feature selection. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to build a radiomics signature. Recurrence prediction models were built using clinicopathological factors and radiomics signature, and a prognostic nomogram was developed and validated by calibration. Results: Among the four radiomics models, the portal venous phase model obtained the best performance in the validation subgroup (C-index = 0.736 (95%CI:0.726-0.856)). When adding the clinicopathological factors to the models, the portal venous phase combined model also yielded the best predictive performance for training (Cindex = 0.792(95%CI:0.727-0.857) and validation (C-index = 0.755(95%CI:0.651-0.860) subgroup. The combined model indicated a more distinct improvement of predictive power than the simple clinical model (ANOVA, P < 0. 0001). Conclusions: This study successfully built a radiomics nomogram that integrated clinicopathological and radiomics features, which can be potentially used to predict ER after curative ablation for HCC patients.

A colorimetric immunoassay is a powerful tool for detecting tumor markers, with outstanding advantages of visualization and convenience. This study designed a colorimetric immunoassay using the antibody/antigen to control the catalytic activity to be "switched on/off". This system, where Au NPs (18.5 ± 3.9 nm) were loaded on the g-C 3 N 4 nanosheets that were fixed in a three-dimensional porous cellulose hydrogel, was used as a binding site for the antibody/antigen. After being incubated with an antibody of a cancer marker, the turned-off catalytic sites on Au NPs in Au@g-C 3 N 4 /microcrystalline cellulose hydrogels would not be "turned on" until the corresponding antigen was added. The number of the recovered Au active sites was related to the amount of the antigen added. The Fourier transform infrared and X-ray photoelectron spectroscopy measurements did not detect the existence of Au−S bonds. Catalyzed by the turned-on Au NPs, 4-nitrophenol was reduced to 4aminophenol accompanied by a color fading. The color and the absorption spectrum changes in the process were used as the colorimetric quantitative basis for immunoassays. The colorimetric immunoassay showed a linear relationship with the liver cancer marker (α-fetoprotein, AFP) in the range of 0.1−10 000 ng/mL with the detection limit of 0.46 ng/mL. In addition, 4nitrophenol had a significant color fading when the AFP concentration exceeded the healthy human threshold. The clinical patient's serum test results obtained from the developed colorimetric immunosensor were consistent with those obtained from the commercial enzyme-linked immunosorbent assay. Furthermore, the immunosensor exhibited a good selectivity, repeatability, and stability, which demonstrated its potential for practical diagnostic application.

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Broad-spectrum detection and long-term monitoring of circulating tumor cells (CTCs) remain challenging due to the extreme rarity, heterogeneity, and dynamic nature of CTCs. Herein, a dual-affinity nanostructured platform was developed for capturing different subpopulations of CTCs and monitoring CTCs during treatment. Stepwise assembly of fibrous scaffolds, a ligand-exchangeable spacer, and a lysosomal protein transmembrane 4 β (LAPTM4B)-targeting peptide creates biomimetic, stimuli-responsive, and multivalent-binding nanointerfaces, which enable harvest of CTCs directly from whole blood with high yield, purity, and viability. The stable overexpression of the target LAPTM4B protein in CTCs and the enhanced peptide–protein binding facilitate the capture of rare CTCs in patients at an early stage, detection of both epithelial-positive and nonepithelial CTCs, and tracking of therapeutic responses. The reversible release of CTCs allows downstream molecular analysis and identification of specific liver cancer genes. The consistency of the information with clinical diagnosis presents the prospect of this platform for early diagnosis, metastasis prediction, and prognosis assessment.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Sorafenib is the standard first‐line systemic chemotherapeutic drugs for advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is frequently observed in clinical practice. In this study, we first produced three sorafenib resistance (SR) HCC cell lines by using two human HCC cell lines (Hep3B and Huh7) and a human primary HCC cell line. We identified that epidermal growth factor receptor (EGFR) and Kruppel‐like factor 4 (KLF4) are dramatically increased in the three SR HCC cell lines. Either inhibition of tyrosine kinase activity of EGFR with Erlotinib/Icotinib or inhibition of KLF4 expression with short hairpin RNA recovered the response of three SR HCC cell lines to sorafenib, suggesting the critical roles of EGFR tyrosine kinase and KLF4 on inducing SR. Luciferase activity and chromatin immunoprecipitation assays further determined that KLF4 promoted EGFR expression through inducing its transcription by directly binding to its promoter. EGFR, conversely, could also promote KLF4 expression through inducing its transcription by binding to its promoter in a tyrosine kinase‐dependent manner, suggesting that a positive feedback loop formed by EGFR and KLF4 further amplifies their effects on inducing SR. Up to now, our findings that KLF4 induces the development of SR and it cooperates with EGFR to form a positive feedback loop to amplify their SR‐inducing abilities have rarely been reported. Our findings bear possible implications for the improvement of the efficacy of sorafenib in HCC.

Background: The higher recurrence rate of hepatocellular carcinoma (HCC) needs to be urgently controlled. However, definitive markers are lacking for patients with recurrence of HCC after undergoing minimal invasive therapies-local ablation combined with transcatheter arterial chemoembolization (TACE). Materials and methods: Demographic and clinicopathological data of 234 subjects receiving combined therapies as the initial treatment were retrospectively analyzed. Univariate and multivariate Cox regression analysis was used to assess independent risk factors of recurrence. Selected variables were divided into low-, intermediate-, and high-risk groups of recurrence according to the scores assigned to them based on their respective hazard ratio (HR) values. The area under the curve (AUC) was used to evaluate the predictive value of the scoring system. Cumulative recurrence-free survival (RFS) and overall survival rates were calculated by the Kaplan-Meier estimator. Finally, a correlation analysis was performed on demographic and clinical data among the three groups. Results: The AUC of predicting 1-, 2-, and 3-year recurrence rates was 0.680, 0.728, and 0.709, respectively. The cumulative RFS rate in the low-risk group at 1, 2, and 3 years after undergoing combined treatments was 4%, 12.2%, and 30.6%, while that in the intermediaterisk group and high-risk group was 23.4%, 51.6%, 60.0%, and 47.3%, 78.2%, 83.6%, respectively. Gamma-glutamyltransferase (γ-GT), blood urea nitrogen (BUN), and total cholesterol (TC) levels among the three groups were statistically different. Conclusion: The scoring system of the present study for patients with the recurrence of HCC after undergoing TACE combined with local ablation may help physicians make a reasonable clinical decision, providing ideal management for diagnosis and treatment.

Hepatocellular carcinomas(HCC) consisted of heterogeneous subtypes with different recurrence probabilities after liver transplantation(LT). Our study aimed to develop an improved model for predicting the recurrence of solitary HCC after LT. In this retrospective study, 151 solitary HCC patients who received orthotopic LT over a period of 10 consecutive years were included. All recipients received graft from deceased donors. The first eligible 50 patients were used as validation cohort and others were utilized to construct the model. A two-tailed P < 0.05 was considered to indicate statistical significance for all analysis. Based on the maximisation of the Youden’s index, the optimal cutoff values for alpha-fetoprotein(AFP) and tumor diameter were 261.6 ng/mL and 3.6 cm, respectively. Vascular involvement includes gross and microscopic vascular invasion. Variables potentially affecting recurrence-free survival(RFS) were examined using univariate and multivariate Cox regression analysis. Univariate and multivariate analysis revealed that AFP, tumor diameter, vascular invasion and cytokeratin-19/glypican-3 sub-typing were independent prognostic factors for RFS, thus comprised the risk scoring model. The AUC values of the model in the cohorts were significantly higher than that of the Milan, UCSF, Fudan and Hangzhou criteria. These findings suggest the model has high performance in predicting early recurrence of solitary HCC patients after LT.