Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Plasmon Coupling and Efficient Charge Transfer in Rough-Surfaced Au Nanotriangles/MXene Hybrids as an Ultrasensitive Surface-Enhanced Raman Scattering Platform.

The rational design of Raman substrate materials with prominent electromagnetic enhancement and charge transfer is quite important for surface-enhanced Raman scattering (SERS). Herein, an efficient SERS substrate based on two-dimensional ultrathin Ti3C2T x MXene and rough-surfaced Au nanotriangles (NTs) was successfully prepared for efficient detection of organic molecules due to the synthetic effect of an optimized electromagnetic field and charge transfer. Uniform Au NTs with tunable surface roughness were controllably prepared by selectively depositing of Au on the smooth Au NTs. Due to the large surface area, tunable plasmon resonance, and abundant hotspots on the planar surface, the modified Au NTs showed much better SERS performance than initial Au NTs. By combination of the rough-surfaced Au NTs with MXene, the Ti3C2T x /Au NT hybrids exhibited much better SERS performance than initial Au NTs and Au NTs with a rough surface. The detection limit is down to 10-12 M, and the analytical enhancement factors reach 3.6 × 109 (at 1174 cm-1) on detecting crystal violet excited at 785 nm. This is because the strong plasmon coupling between the in-plane resonance of Au NTs and transversal plasmon resonance of Ti3C2T x MXene around 785 nm can generate an intense interfacial electromagnetic field for amplifying SERS signals. Additionally, the efficient charge transfer between Au NTs, MXene, and molecules also plays an important role in enhancing the SERS performance. This work presents a new insight to develop high-performance SERS substrates based on plasmon.

Construction of a novel immune-related lncRNA signature and its potential to predict the immune status of patients with hepatocellular carcinoma.

BACKGROUND: The accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC. METHODS: In this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy. RESULTS: A total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients. CONCLUSIONS: The nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

Strong Visible Light Absorption and Abundant Hotspots in Au-Decorated WO3 Nanobricks for Efficient SERS and Photocatalysis.

Metal/semiconductor hybrids show potential application in fields of surface-enhanced Raman spectroscopy (SERS) and photocatalysis due to their excellent light absorption, electric field, and charge-transfer properties. Herein, a WO3-Au metal/semiconductor hybrid, which was a WO3 nanobrick decorated with Au nanoparticles, was prepared via a facile hydrothermal method. The WO3-Au hybrids show excellent visible light absorption, strong plasmon coupling, high-performance SERS, and good photocatalytic activity. In particular, on sensing rhodamine B (RhB) under 532 nm excitation, bare WO3 nanobricks have a Raman enhancement factor of 2.0 × 106 and a limit of detection of 10-8 M due to the charger-transfer property and abundant oxygen vacancies. WO3-Au metal/semiconductor hybrids display a largely improved Raman enhancement factor compared to pure Au and WO3 components owing to the synergistic effect of electromagnetic enhancement and charge transfer. The Raman enhancement factor and limit of detection are further improved, reaching 5.3 × 108 and 10-12 M, respectively, on increasing the content of Au to 2.1 wt %, owing to the strong plasmon coupling between the Au nanoparticles. Additionally, the WO3-Au hybrids also exhibit excellent photocatalytic activity toward degradation of RhB under visible light irradiation. WO3-Au (2.1 wt %) possesses the fastest photocatalytic rate, which is 6.1 and 2.0 times that of pure WO3 nanobricks and commercial P25, respectively. The enhanced photocatalytic activity is attributed to the strong plasmon coupling and the efficient charge transfer between Au and WO3 nanobricks. The as-prepared materials show great potential in detecting and degrading pollutants in environmental treatment.

Plasmon-Mediated 2D/2D Phase Junction for Improved Photocatalytic Hydrogen Generation Activity.

A phase junction fabricated by two crystalline phases of the same semiconductor is a promising photocatalyst with efficient charge transfer and separation. However, the weak light absorption and uncontrolled phase junction interface limit the generation and separation of photogenerated carriers. Herein, a two-dimensional (2D)/2D phase junction was prepared by growing orthorhombic WO3 ultrathin nanosheets on hexagonal WO3 nanosheets through a one-step hydrothermal method. The orthorhombic/hexagonal WO3 possesses large-area phase junction interfaces, rich reactive sites, and built-in electric field, which greatly accelerate the photogenerated charge separation and transfer. Thus, the orthorhombic/hexagonal WO3 displayed excellent photocatalytic hydrogen generation activity from water splitting under light irradiation (λ > 420 nm), which is 2.16 and 2.85 times those of orthorhombic and hexagonal WO3 phase components. Furthermore, Au nanoparticles (about 4.5 nm in diameter) were deposited on both orthorhombic and hexagonal WO3 nanosheets to form a plasmon-mediated phase junction. The hybrids exhibit prominent visible-light absorption and efficient charge transfer, leading to a further improved photocatalytic hydrogen generation activity. Further characterization studies demonstrate that superior photoactivity arises from the excellent visible-light-harvesting ability, appropriate band structure, and high-efficiency and multichannel transferring processes of photogenerated carriers.

Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.

Comparison of the Prognostic Value of Inflammation-Based Scores in Patients with Hepatocellular Carcinoma After Anti-PD-1 Therapy.

BACKGROUND: Inflammatory response is related to cancer progression and patient survival. However, the value in predicting survival in hepatocellular carcinoma (HCC) patients who received anti-PD-1 therapy has not been elucidated. This study aimed to compare the predictive ability of inflammation-based scores for the prognosis of HCC patients after anti-PD-1 therapy. METHODS: A total of 442 patients who received anti-PD-1 therapy were included in the study. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan-Meier survival curves, time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses. RESULTS: All the inflammation-based prognostic scores exhibited good discriminatory ability in overall survival (OS) (all P < 0.01), while the PNI score was a unique independent predictor for OS in multivariate analysis (hazard ratio, 1.770; confidence interval, 1.309-2.393; P < 0.001). The areas under the ROC curves at 6, 12, 18 and 24 months and the C-index (0.65) demonstrated that the predictive accuracy of the PNI score was superior to that of the other inflammation-based scores. CONCLUSION: The PNI score is a discriminatory prognostic indicator for OS in HCC patients with anti-PD-1 therapy and is superior to the other inflammation-based prognostic scores in terms of predictive ability.

Lymphocyte-C-reactive protein ratio as a novel prognostic index in intrahepatic cholangiocarcinoma: A multicentre cohort study.

BACKGROUND & AIMS: The lymphocyte-C-reactive protein ratio (LCR) is a novel inflammatory-based score, based solely on the lymphocyte and C-reactive protein. We aimed to clarify the prognostic value of the LCR score in intrahepatic cholangiocarcinoma (ICC) patients after resection. METHODS: We compared the prognostic accuracy of the LCR score with other inflammatory-based scores in this large, multicentre cohort study. The independent variables associated with overall survival (OS) were explored in both the primary (n = 228) and validation cohorts (n = 135). Harrell's concordance index (C-index) was used to compare the predictive ability of all the assessed inflammatory-based scores. RESULTS: The LCR score was differentiated two groups of ICC patients with distinct prognoses (1-, 3-, and 5-year OS rates: 94.4%, 66.3%, and 59.3%; and 66.6%, 45.6%, and 32.7%, respectively) (P < .001). Multivariate analysis showed that the LCR score, as well as the TNM stage and preoperative CA19-9 level, were independently associated with OS. The predictive accuracy of the LCR score (c score: 0.634) was superior to that of the other inflammatory-based scores (c scores: 0.508-0.615). These findings were supported by the external validation cohort. CONCLUSION: The LCR score is stable and consistently the best prognostic score and may offer as a simple, objective and discriminatory method in facilitating the risk stratification of ICC patients.

Resection vs. Sorafenib for Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Real World, Propensity Score Matched Analytic Study.

Background: Macroscopic vascular invasion (MVI) commonly occurs in patients with advanced hepatocellular carcinoma (HCC) for which resection and sorafenib are the common therapies prescribed. Here, we aimed to compare the survival outcomes of these two therapies in HCC patients with MVI. Methods: In total, 496 patients diagnosed with HCC and MVI without extrahepatic metastasis, treated with resection (resection-based group, n = 388) and sorafenib (sorafenib-based group, n = 108) were included in this study. A one-to-one propensity score-matching analysis (PSM) was performed to minimize the effect of potential confounders. Results: The median OS in the resection- and sorafenib-based group was 20.7 months (95% CI: 16.9-24.5) and 11.6 months (95% CI: 8.4-14.9) (p < 0.001), respectively. The median PFS was 4.7 months (95% CI: 3.8-5.5) in the resection-based group and 4.4 months (95% CI: 3.6-5.2) in the sorafenib-based group (p < 0.001). After PSM, 72 patients from each group were matched. The median OS was 27.2 months (95% CI: 16.4-38.0) in the resection-based group and 13.0 months (95% CI: 9.6-16.3) in the sorafenib-based group (p < 0.001). The median PFS was 5.3 months (95% CI: 3.2-7.4) in the resection-based group and 4.8 months (95% CI: 3.6-6.0) in the sorafenib-based group (p = 0.061). Conclusion: Findings from this study showed that, compared with sorafenib-based treatment, surgical resection might be associated with better survival benefits to HCC patients with MVI.