Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis.

Objective: To evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT). Patients and methods: From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups. Results: The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028). Conclusion: This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.

Development and validation of a novel glycolysis-related risk signature for predicting survival in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is one of the leading causes of cancer-related deaths worldwide. Through data mining, an increasing number of biomarkers have been identified to predict the survival of patients with PAAD. However, the ability of single gene biomarkers to predict patient survival is still insufficient. This study aimed to develop a novel risk signature for predicting the survival of patients with PAAD. METHODS: mRNA expression profiling was performed for a large PAAD cohort (n = 177) identified using The Cancer Genome Atlas database (TCGA). Gene set enrichment analysis (GSEA) was performed to detect whether the gene sets showed significant differences between PAAD and adjacent normal tissues. Univariate Cox regression was used to analyze and identify genes related to overall survival (OS). Multivariate Cox regression was subsequently used to confirm the prognostic genes and obtain the coefficients. By analyzing the expression level of selected genes weighted by their coefficients through linearly combining, we constructed a risk score formula for prognostic prediction. The three-mRNA signature for survival prediction was validated using the Kaplan-Meier method. RESULTS: We demonstrated that a set of three genes (KIF20A, CHST2, and MET) were significantly associated with OS. Based on this three-gene signature, 177 PAAD patients were classified into high-risk and low-risk groups using the median risk score as the cut-off value. We also validated the reliability of this three-gene signature in the GSE28735 dataset from the Gene Expression Omnibus (GEO) database. Additionally, multivariate Cox regression analysis revealed that the three-gene signature had an independent prognostic value. CONCLUSION: To the best of our knowledge, this is the first study to develop a glycolysis-related risk signature for predicting the survival of patients with pancreatic adenocarcinoma. Our findings provide insight into the identification of PAAD patients with poor prognosis. We also identified novel therapeutic targets for this disease.

Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression.

Long non-coding RNAs (LncRNAs) have been suggested as important regulators of cancer development and progression in non-small cell lung cancer (NSCLC). Nevertheless, the biological roles and clinical significance of lncRNA UFC1 in NSCLC remain unclear. We detected the expression of UFC1 in tumor tissues, serum, and serum exosomes of NSCLC patients by qRT-PCR. Gene overexpression or silencing were used to examine the biological roles of UFC1 in NSCLC. RNA immunoprecipitation and ChIP assays were performed to evaluate the interaction between UFC1 and enhancer of zeste homolog 2 (EZH2) and the binding of EZH2 to PTEN gene promoter. Rescue study was used to access the importance of PTEN regulation by UFC1 in NSCLC progression. UFC1 expression was upregulated in tumor tissues, serum, and serum exosomes of NSCLC patients and high level of UFC1 was associated with tumor infiltration. UFC1 knockdown inhibited NSCLC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. UFC1 overexpression led to the opposite effects. Mechanistically, UFC1 bound to EZH2 and mediated its accumulation at the promoter region of PTEN gene, resulting in the trimethylation of H3K27 and the inhibition of PTEN expression. UFC1 knockdown inhibited NSCLC growth in mouse xenograft tumor models while the simultaneous depletion of PTEN reversed this effect. NSCLC cells derived exosomes could promote NSCLC cell proliferation, migration and invasion through the transfer of UFC1. Moreover, Exosome-transmitted UFC1 promotes NSCLC progression by inhibiting PTEN expression via EZH2-mediated epigenetic silencing. Exosome-mediated transmit of UFC1 may represent a new mechanism for NSCLC progression and provide a potential marker for NSCLC diagnosis.

Effectiveness and safety of irreversible electroporation for recurrent hepatocellular carcinoma ineligible for thermal ablation after surgery.

OBJECTIVES: To preliminarily evaluate the clinical effectiveness and safety of computed tomography (CT) image-guided irreversible electroporation (IRE) for the treatment of recurrent hepatocellular carcinoma (HCC) after surgical resection. METHODS: From January 2016 to February 2018, 18 patients diagnosed with recurrent HCC after surgical resection received IRE under CT image guidance for 22 tumors. Patients were enrolled for IRE when ineligible for thermal ablation due to tumor location. Clinical records and imaging data were reviewed to assess complete ablation rate, local tumor progression free rate (LTPFR), local tumor progression free survival (LTPFS) and complications after a median follow-up time of 14 months. RESULTS: Successful complete ablations were achieved in 20/22 (90.1%) tumors. Mean LTPFS was 10.5 â€‹± â€‹9.4 months. Overall 3-, 6- and 12-months LTPFR in 22 tumors following IRE were 68.2% (95% confidence interval [CI]: 45%-83%), 59.1% (95% CI: 33%-76%) and 36.4% (95% CI: 17%-56%), respectively. Complications included pneumothorax (2/18, 11.1%), localized pain (3/18, 16.7%), bile duct dilation (1/18, 5.6%) and transient hypertension (1/18, 5.6%). No major complications or treatment-related deaths were observed. The alpha-fetoprotein levels of two patients decreased to the normal range at 3 and 4 months, respectively. CONCLUSIONS: This study showed that percutaneous CT image-guided IRE can serve as a safe and effective treatment for recurrent HCC not suitable for thermal ablation.

Long non-coding RNA DANCR promotes the progression of non-small-cell lung cancer by inhibiting p21 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in human cancers. However, the functional roles of lncRNAs in non-small-cell lung cancer (NSCLC) and the underlying mechanisms are not well understood. METHODS: We examined the expression of lncRNA DANCR in NSCLC by qRT-PCR and explored its biological roles in NSCLC progression by cell and molecular biology studies. RESULTS: DANCR expression level was increased in human NSCLC. The knockdown of DANCR inhibited NSCLC cell proliferation by inducing cell apoptosis and cell cycle arrest. In addition, DANCR knockdown suppressed NSCLC cell migration and invasion via inhibition of epithelial-mesenchymal transition (EMT). On the contrary, DANCR overexpression had the opposite effects. DANCR knockdown inhibited EZH-2-mediated epigenetic silencing of p21 promoter and increased p21 expression. Moreover, DANCR knockdown inhibited NSCLC cell proliferation, migration, and invasion in a p21-dependent manner. CONCLUSION: DANCR plays oncogenic roles in NSCLC and may provide a novel biomarker for NSCLC diagnosis and prognosis.

Nucleolar spindle associated protein 1 (NUSAP1) facilitates proliferation of hepatocellular carcinoma cells.

BACKGROUND: The most fundamental characteristic of cancer cells is abnormal proliferation, which is partly due to deregulation of cell cycle. Nucleolar spindle associated protein 1 (NUSAP1) is originally identified as microtubule and chromosome binding protein and takes an important role in chromosome segregation fidelity. Recent studies have been documented that NUSAP1 is associated with the progression of several cancers. However, its expressions and functions are unclear in hepatocellular carcinoma (HCC). METHODS: qPCR and western blotting were used to examine NUSAP1 levels in fresh paired HCC tissues and corresponding adjacent normal liver tissues (ANT). MTT and colony formation assay were performed to evaluate whether NUSAP1 can influence the proliferation of HCC cells. Anchorage-independent growth assay was implemented to detect the effect of NUSAP1 on in vitro tumorigenicity capacity. Flow cytometry, qPCR and western blotting assay were used to clarify the detailed mechanisms that NUSAP1 accelerates the capability for cell proliferation and in vitro tumorigenicity. RESULTS: Firstly, we analyzed the availably public dataset The Cancer Genome Atlas (TCGA), and discovered that NUSAP1 is dramatically upregulated in HCC tissues and closely correlated with poor prognosis of patients suffering HCC, which was confirmed in fresh HCC tissues and ANT. Subsequently, cell function assay illustrated that the upregulation of NUSAP1 facilitates proliferation and in vitro tumorigenicity capacity of HCC cells. Besides, molecular experiments suggested that NUSAP1 promotes cell cycle transition of HCC cells. CONCLUSIONS: In summary, the above results inferred that NUSAP1 takes an indispensable role in cell cycle progression. And it might be served as a novel prognostic factor in HCC.

Transcatheter hepatic arterial infusion chemotherapy vs sorafenib in the treatment of patients with hepatocellular carcinoma of Barcelona Clinic Liver Cancer stage C: a meta-analysis of Asian population.

OBJECTIVE: To compare the clinical efficacy and safety of transcatheter hepatic arterial infusion chemotherapy (HAIC) with those of sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C. METHODS: Potentially relevant studies comparing the clinical efficacy and safety of HAIC with those of sorafenib were searched using Medline, PubMed, Embase, Cochrane Library, and Chinese databases (Wanfang Data and China National Knowledge Infrastructure). Overall survival rate (OSR), tumor response rate, disease control rate (DCR), and serious adverse events (SAEs) were compared and analyzed. Pooled ORs with 95% CIs were calculated using either the fixed-effects model or the random-effects model. All statistical analyses were conducted using Review Manager (version 5.3) from the Cochrane Collaboration. RESULTS: A total of 1,264 patients were included in this meta-analysis. The results of this study showed that HAIC was associated with significantly higher 1-, 2-, and 3-year OSRs than sorafenib (OR 1.88, 95% CI1-year: [1.27-2.78], P1-year=0.002; OR 2.15, 95% CI2-year: [1.06-4.37], P2-year=0.03; OR 7.90, 95% CI3-year: [2.12-29.42], P3-year=0.002). Compared to sorafenib, HAIC was associated with superior complete response (CR), partial response (PR), and objective response rate (ORR) (OR 3.90, 95% CICR: [1.89-8.03], P CR =0.0002; OR 3.47, 95% CIPR: [2.31-5.24], P PR <0.00001; OR 3.02, 95% CIOR: [2.05-4.45], P OR <0.0001). There was no statistically significant difference between HAIC and sorafenib in stable disease (SD), progressive disease (PD), DCR, and SAEs (OR 0.86, 95% CISD: [0.51-1.45], P SD =0.56; OR 0.62, 95% CIPD: [0.35-1.11], P PD =0.11; OR 0.53, 95% CISAE: [0.14-1.92], P SAE =0.33). CONCLUSION: This study showed that HAIC was associated with better efficacy than sorafenib in terms of OSR and tumor response. Therefore, HAIC can be considered as an alternative treatment option for patients with HCCs of BCLC stage C.

Radiofrequency ablation combined with transcatheter arterial chemoembolization therapy versus surgical resection for Barcelona-Clinic Liver Cancer (BCLC) A hepatocellular carcinoma: a meta-analysis.

Purpose: The objective of our study was to compare the effectiveness of the combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) with that of surgical resection (SR) in Barcelona-Clinic Liver Cancer (BCLC) A hepatocellular carcinoma. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for comparisons of the two therapies from January 2006 to December 2017. Overall survival rate (OS), recurrence-free survival rate (RFS), complications, and the average length of hospital stay were compared and analyzed. Review Manager v. 5.2 from the Cochrane Collaboration was used for statistical analyses. Results: Seven case-control studies and one randomized controlled trial were identified, of which 717 were treated with a combination of TACE and RFA and 785 were treated with SR. Meta-analysis data revealed that TACE plus RFA had significantly better effectiveness on 1.0-y OS (OR = 0.50, p = .009). The major complications (ORcomplications = 1.88, p = .02) after the combined therapy were significantly lower than those after SR. There were three studies that reported the average length of hospital stay. The hospital stay for the SR group vs the combined therapy group was 19.8 ± 8.4 d vs 7.4 ± 2.2 d, respectively (p < .0001); 18.7 ± 4.9 d vs 11.5 ± 6.9 d, respectively (p < .0001); and 16.6 ± 6.7 d vs 8.5 ± 4.1 d, respectively (p < .0001). There was no significant difference in 3.0- or 5.0-y OS and 1.0-, 3.0-, or 5.0-y RFS. Conclusion: The combination of TACE and RFA has advantages in improving 1.0-y OS, reducing complications, and shortening the length of hospital stay over that of SR in the treatment of patients with BCLC A HCC.