AimA programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy.MethodsIn this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China).ResultA total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1+ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1+ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1+ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1+ CTC counts at 1 month after treatment.ConclusionsOur study demonstrated that PD-L1+ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.

Background Selective internal radiation therapy (SIRT) is a developing technique and its efficacy and modality of application in hepatocellular carcinoma (HCC) are still controversial. This network meta-analysis aims to determine whether the efficacy and safety of SIRT alone and in combination are superior to that of sorafenib. Methods Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched before August 2022. Cochrane Randomized Trial Risk of Bias Assessment Tool and the Newcastle–Ottawa scale were used to assess the quality. The outcomes of interest included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Results A total of 9 eligible trials involving 1954 patients were included, and SIRT ranked first among the three treatment modalities in terms of both OS (probability, 52.3%) and PFS (probability, 68.6%). The combination of SIRT and sorafenib did not improve OS or PFS in patients with HCC. Although the combination of SIRT and sorafenib did not raise the risk of grade 3 or higher AEs, it may have introduced more AEs than either alone. Conclusions SIRT alone was found to be superior to sorafenib and the combination of the two in improving OS or PFS in patients with non-surgical HCC, especially in patients with combined portal vein tumor thrombus. The AEs induced by SIRT were different from those of sorafenib, but the overall toxicity was manageable, the combination of the two may cause an increase in the types of AEs that occur.

Purpose In the treatment of advanced hepatocellular carcinoma (HCC), programmed death-1 (PD-1) immune checkpoint inhibitors has recently been shown to be highly effective when combined with radiotherapy. Furthermore, they have become the hotspot in cancer diagnosis and treatment for the detection of programmed death-ligand 1 (PD-L1) in circulating tumor cells (CTCs). However, their predictive effect is not well established. Therefore, this study examined whether PD-L1 expression in CTCs can be used as a marker to predict treatment response in patients with advanced HCC. Methods Patients treated with both PD-1 inhibitors and intensity-modulated radiation therapy (IMRT) were enrolled in the study. After radiation therapy, PD-1 inhibitor treatment was administered every 3 weeks until disease progression. Peripheral blood (2 mL) was collected from patients before and after treatment, and CTC PD-L1 was detected using the Watson Biotechnology reagent (China). Results A total of 28 patients with HCC were enrolled in this study. The disease control rate (DCR) was significantly higher in patients with PD-L1(+) CTC enrichment at baseline than in controls (92.3% and 50%, respectively). Before treatment, patients with PD-L1(+) CTCs ≥ 2 had a higher median progression-free survival (mPFS) than those with PD-L1(+) CTCs ≤ 1 (3.50 vs. 3.35 months). After treatment, CTCs with PD-L1(+) ≤ 1 were significantly associated with longer mPFS than CTCs with PD-L1(+) ≥ 2 (4.20 vs. 1.90 months, P < 0.01). Conclusions The presence of CTCs expressing PD-L1(+) might predict efficacy and prognosis in HCC patients treated with PD-1 inhibitors and radiotherapy. Retrospectively registered The study has been registered with the Chinese Clinical Trials Registry (registration number: ChiCTR2100044198).

Background. LINC00922 has been found to promote epithelial-mesenchymal transition (EMT) in a variety of tumors. But its functions in gastric cancer (GC) remain unclear. We attempt to investigate the correlation between LINC00922 and GC via bioinformatics analysis, in vitro and in vivo experiments. Methods. TCGA and GTEx databases were utilized to obtain the RNAseq and clinical data of GC, and then, identified the correlation of LINC00922 with patients’ clinicopathological characteristics and prognosis. GSEA and GO/KEGG enrichment analyses were performed to explore the potential functions or signaling pathways that LINC00922 participated in GC. Infiltration levels of immune cells were employed by ssGSEA algorithm, and then Wilcoxon rank sum test was applied to analyze their correlations with LINC00922. Scratch and transwell assays were conducted to detect the invasion and migration abilities of GC cells. Western blot was performed to explore the expression level of EMT-related proteins. Furthermore, we constructed the xenograft tumor model and metastatic tumor model in nude mice to explore the effect of LINC00922 downregulating on metastasis of GC cells in vivo. Results. Compared with normal tissues, LINC00922 was highly expressed in GC tissues and positively correlated with poor prognosis. The correlation existed between LINC00922 and immune infiltration in GC. Downregulation of LINC00922 inhibited the EMT process of GC cells. In addition, both in vitro and in vivo experiments showed that LINC00922 affects the invasion and migration abilities of GC. Conclusions. LINC00922 promotes the migration, invasion, and EMT in GC and has the potential to be used as a prognostic biomarker and therapeutic target for GC.