Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study.

Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan-Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan-Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.

Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. METHODS: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. RESULTS: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. CONCLUSIONS: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

Clinical Characteristics of Patients With Progressive and Non-progressive Coronavirus Disease 2019: Evidence From 365 Hospitalised Patients in Honghu and Nanchang, China.

Background: Coronavirus disease (COVID-19) has swept around the globe and led to a worldwide catastrophe. Studies examining the disease progression of patients with non-severe disease on admission are scarce but of profound importance in the early identification of patients at a high risk of deterioration. Objectives: To elucidate the differences in clinical characteristics between patients with progressive and non-progressive COVID-19 and to determine the risk factors for disease progression. Study design: Clinical data of 365 patients with non-severe COVID-19 from 1 January 2020 to 18 March 2020 were retrospectively collected. Patients were stratified into progressive and non-progressive disease groups. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for disease progression. Results: Compared with patients with non-progressive disease, those who progressed to severe COVID-19 were older and had significantly decreased lymphocyte and eosinophil counts; increased neutrophil and platelet counts; lower albumin levels; higher levels of lactate dehydrogenase, C-reactive protein (CRP), creatinine, creatinine kinase, and urea nitrogen; and longer prothrombin times. Hypertension, fever, fatigue, anorexia, bacterial coinfection, bilateral patchy shadowing, antibiotic and corticosteroid administration, and oxygen support had a significantly higher incidence among patients with progressive disease. A significantly longer duration of hospital stay was also observed in patients with progressive disease. Bilateral patchy shadowing (OR = 4.82, 95% CI: 1.33-17.50; P = 0.017) and elevated levels of creatinine (OR =6.24, 95% CI: 1.42-27.40; P = 0.015), and CRP (OR = 7.28, 95% CI: 2.56-20.74; P < 0.001) were independent predictors for disease progression. Conclusion: The clinical characteristics of patients with progressive and non-progressive COVID-19 were significantly different. Bilateral patchy shadowing and increased levels of creatinine, and CRP were independent predictors of disease progression.