Upregulation of lncRNA PTOV1-AS1 in hepatocellular carcinoma contributes to disease progression and sorafenib resistance through regulating miR-505.

Increasing evidence has displayed the vital influence of lncRNA in tumorigenesis and chemoresistance of cancer treatment. This study investigated the function of lncRNA PTOV1-AS1 in hepatocellular carcinoma (HCC) and its role in sorafenib resistance. The relative expression of lncRNA and miRNA was measured by RT-qPCR. The cellular activities including cell proliferation and invasion were explored by CCK-8 and Transwell assays. Bioinformatics analysis and dual-luciferase reporter assay were used to predict the targeting miRNA of PTOV1-AS1. The expression levels of PTOV1-AS1 were higher in HCC tissues than that in the normal tissues and associated with patients' overall survival. Knockdown of PTOV1-AS1 decreased cell proliferation rate and invasion number. After treatment with different concentrations of sorafenib, the sorafenib-resistant hepatoma cells were conducted. PTOV1-AS1 expression levels were increased in HepG2-SR and Huh7-SR cells. PTOV1-AS1 knockdown repressed the proliferation, invasion, and drug resistance of sorafenib-resistant HCC cells by targeting the expression of miR-505. In conclusion, the expression of PTOV1-AS1 is increased in HCC and sorafenib-resistance HCC cells, as well as is associated with patients' prognosis. Inhibition of PTOV1-AS1 expression can reduce the resistance of sorafenib-resistant HCC cells, which may play a role by targeting the negative regulation of miR-505 expression.

Toripalimab in combination with Anlotinib for unresectable hepatocellular carcinoma after SBRT: A prospective, single-arm, single-center clinical study.

Objective: Exposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT. Methods: This is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0-1, Child-Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the Kaplan-Meier method. Categorical data were expressed as n (percentage). Results: Between June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%. Conclusion: Exposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration. Clinical trial registration: www.clinicaltrials.gov, identifier ChiCTR2000032533.