Development and Validation of a Propionate Metabolism-Related Gene Signature for Prognostic Prediction of Hepatocellular Carcinoma.

Background: Studies have demonstrated that propionate metabolism-related genes (PMRGs) are associated with cancer progression. PMRGs are not known to be involved in Hepatocellular carcinoma (HCC). Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were accessed for HCC-related transcriptome data and clinical information. First, DE-PMRGs were derived by intersecting PMRGs and DEGs between HCC tissues and normal controls. The clusterProfiler R package was then used to enrich DE-PMRGs. In addition, biomarkers of HCC were identified, and a prognostic model was developed. Using functional analysis and tumor microenvironment analysis, new insights were obtained into HCC. The expression of biomarkers was validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: 132 DE-PMRGs were obtained by intersecting 3690 DEGs and 291 PMRGs. Steroid and organic acid metabolism were associated with these genes. For the construction of the risk model for HCC samples, five biomarkers were identified, including Acyl-CoA dehydrogenase short chain (ACADS), CYP19A1, formiminotransferase cyclodeaminase (FTCD), glucose-6-phosphate dehydrogenase (G6PD), and glutamic-oxaloacetic transaminase (GOT2). ACADS, FTCD, and GOT2 were positive factors, whereas CYP19A1 and G6PD were negative. HCC patients with AUC greater than 0.6 were predicted to survive 1/2/3/4/5 years, indicating decent efficiency of the model. The probability of 1/3/5-survival for HCC was also predicted by the nomogram using the risk score, pathologic T stage, and cancer status. Moreover, functional enrichment analysis revealed the high-risk genes were associated with invasion and epithelial-mesenchymal transition. Significantly, immune cell infiltration and immune checkpoint expression were linked to HCC development. Conclusion: This study identified five biomarkers of propionate metabolism that can predict HCC prognosis. This finding may provide a deeper understanding of PMRG function in HCC.

Circ_0001686 knockdown suppresses tumorigenesis and enhances radiosensitivity in esophagus cancer through regulating miR-876-5p/SPIN1 axis.

BACKGROUND: Abnormal expression of circular RNAs (circRNAs) plays an important role in tumorigenesis and radiosensitivity of many cancers. Nevertheless, it is not clear whether circ_0001686 is associated with the development and radiosensitivity of esophagus cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0001686, microRNA-876-5p (miR-876-5p) and spindlin 1 (SPIN1). Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry and transwell assay were applied to evaluate cell viability, cell proliferation, cell apoptosis and cell invasion capacities. Radiosensitivity was monitored by colony formation assay. The target relationship between miR-876-5p and circ_0001686 or SPIN1 was identified by dual-luciferase reporter assay. The protein level of SPIN1 was measured by western blot assay. Xenograft tumor models were used to analyze the influence of circ_0001686 on radiosensitivity and tumor growth in vivo. RESULTS: The expression levels of circ_0001686 and SPIN1 were increased, while miR-876-5p was decreased in esophagus cancer tissues and cells. Interference of circ_0001686 constrained cell proliferation and invasion, but promoted cell apoptosis and radiosensitivity. Additionally, miR-876-5p was the target of circ_0001686 and miR-876-5p inhibition effectively ameliorated the impacts of circ_0001686 deficiency on tumorigenesis and radiosensitivity. Moreover, SPIN1 was a direct target of miR-876-5p and SPIN1 overexpression partially overturned the effects of miR-876-5p transfection on tumor progression and radiosensitivity. Importantly, circ_0001686 could sponge miR-876-5p to regulate SPIN1 expression. In addition, circ_0001686 silencing also constrained tumor growth and increased radiosensitivity in vivo. CONCLUSION: Circ_0001686 contributed to the progression and radioresistance of esophagus cancer cells via regulating SPIN1 expression by targeting miR-876-5p, providing a new therapeutic target for improving the prognosis of esophagus cancer patients.

Hsa_circ_0007380 silencing restrains the growth and enhances radiosensitivity in esophagus cancer by miR-644a/Spindlin 1 axis.

Circular RNAs are frequently dysregulated and show important regulatory function of tumorigenesis in cancers. Hsa_circ_0007380 was found to be elevated in human radioresistant esophageal cancer cells. Here, this study aimed to investigate the action and mechanism of hsa_circ_0007380 in esophageal cancer carcinogenesis and radiosensitivity. Quantitative real-time PCR and western blotting were performed to detect levels of genes and proteins. Functional experiments were conducted using MTT assay, EdU assay, clonogenic survival assay, flow cytometry and murine xenograft model assay, respectively. The binding between miR-644a and hsa_circ_0007380 or spindlin1 (SPIN1) was validated using dual-luciferase activity assay. Hsa_circ_0007380 was highly expressed in esophagus cancer tissues and cells, knockdown of hsa_circ_0007380 suppressed esophagus cancer cell proliferation, induced apoptosis and enhanced radiosensitivity in vitro, and the same effects were also confirmed in nude mice. Mechanistically, hsa_circ_0007380 sequestered miR-644a to release SPIN1 expression, implying the hsa_circ_0007380/miR-644a/SPIN1 competing endogenous RNA network esophagus cancer cells. miR-644a was decreased in esophagus cancer, re-expression of miR-644a restrained cell growth and conferred radiosensitivity in esophagus cancer, which were reversed by SPIN1 overexpression. Besides that, inhibition of miR-644a abolished the promoting action of hsa_circ_0007380 knockdown on esophagus cancer apoptosis and radiosensitivity. Hsa_circ_0007380 silencing impedes cell growth and reinforces radiosensitivity in esophagus cancer by miR-644a/SPIN1 axis, suggesting a promising therapeutic target for esophagus cancer combined treatment.

Embolization of hepatic arterioportal shunt with ethanol-soaked gelatin sponge.

OBJECTIVE: The objective of this study is to investigate the effect of ethanol-soaked gelatin sponge (ESG) in the treatment of hepatic arterioportal shunt (APS). METHODS: Hepatocellular carcinoma (HCC) patients with APS were divided into experimental group (Group E) and control group (Group C). Patients in Group E were treated with ESG for APS embolization, whereas patients in Group C were treated with polyvinyl alcohol particles for APS embolization, with other treatment unchanged. APS and the Eastern Cooperative Oncology Group (ECOG) physical status scores of patients before and after the first treatment and further consultation in the 6th week and the survival rate in follow-up visit were recorded. The changes of liver function during treatment were monitored. RESULTS: Before the first treatment, there was no statistical significant difference in APS between two groups. After that, APS in Groups E (P = 2.49 × 10-7) and C (P = 2.10 × 10-4) was improved. In further consultation, APS in Groups E (P = 2.73 × 10-13) and C (P = 2.90 × 10-8) was further improved after examinations and corresponding treatment. After the first treatment and further consultation, APS score was lower in Group E than in Group C, and there were still five patients whose APS score was 2 in Group C. Quality of life in two groups was effectively controlled without getting worse and the ECOG score reduced. Liver function in the two groups did not worsen with the use of liver protective drugs. No deaths occurred in Group E, whereas two patients died in Group C during treatment and follow-up visit. CONCLUSION: The results show that ESG can effectively reduce APS score and improve the survival rate of HCC patients.

Sorafenib improves lipiodol deposition in transarterial chemoembolization of Chinese patients with hepatocellular carcinoma: a long-term, retrospective study.

OBJECTIVE: Though synergy of sorafenib and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is well discussed in previous reports, association of lipiodol retention by sorafenib addition to TACE with the survival outcomes remain elusive. Therefore, we studied the impact of sorafenib addition to TACE on survival outcomes mediated by lipiodol retention. MATERIALS AND METHODS: This is a long-term, retrospective, single-center study using medical records of patients diagnosed with HCC at the Department of Interventional Radiology of Zhengzhou University Affiliated Cancer Hospital (China) between April 2004 and March 2012. RESULTS: Lipiodol deposition of > 50% was significantly increased in TACE + sorafenib group (70.87%) compared to TACE alone group (45.11%) (P = 0.0001). Significant increase in lipiodol deposition with sorafenib treatment was observed compared to TACE alone group (OR = 0.449, P = 0.041). The median overall survival in TACE + sorafenib and TACE alone groups were 38 months [95% CI = 9.772-56.228] and 31 months [95% CI = 21.855-40.145] respectively. Also, the hazard of death was comparatively greater in TACE alone group than TACE + sorafenib group [HR = 1.071]. Response rate to the therapy significantly increased after sorafenib administration to TACE patients, [compared to TACE alone treatment [69/103 (66.99%)] vs 55/133 (41.35%)], P = 0.0001. CONCLUSIONS: Lipiodol deposition is significantly increased upon sorafenib addition after TACE. However, there was no significant impact of lipiodol deposition on the survival benefits exerted by the synergistic combination and hence, future prospective trails are warranted to validate the findings of this study.

Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism.

OBJECTIVE: To investigate the influence of lactulose on immunity of hepatocellular carcinoma (HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. METHODS: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 mL/d. Four days before interventional therapies and at days 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count (RBC), and platelet count (PLT). Four days before therapies and at days 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase (SOD), IFN-γ, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. RESULTS: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency (P < 0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-γ and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group (P < 0.05), the levels of CD4(+)/CD8(+), SOD and IFN-γ were all higher than before and control group (P < 0.05). CONCLUSIONS: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

Tumor vascularity and lipiodol deposition as early radiological markers for predicting risk of disease progression in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization.

This study evaluated the factors impacting overall survival (OS) and time to progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). HCC patients were grouped based on tumor vascularity and lipidiol deposition after TACE. Tumor vascularity was classified based on contrast enhancement on arterial phase baseline CT scans. Lipiodol deposition was evaluated using CT scans. The progression-free rate was significantly higher in patients with good blood supply + good lipiodol deposition compared to those with good blood supply + poor lipiodol deposition. In patients with poor lipidiol deposition, risk of death was significantly positively correlated with stage, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Risk of disease progression in these patients was positively correlated with tumor size, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Our data showed that tumor vascularity and lipiodol deposition can be used as early radiological markers to identify patients who do not respond to TACE, and who can be considered earlier for alternative combination treatment strategies. Our data also indicated that poor lipiodol retention may predict a poor TTP and OS despite the blood supply status.

[The clinical therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization in treating primary liver cancer with pulmonary metastases].

OBJECTIVE: To observe the therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization on treatment of primary liver cancer with pulmonary metastases. METHODS: Sixty patients were randomly divided into two groups: group A (treatment group, n = 30) and group B (control group, n = 30). Group A was received periodic transcatheter arterial chemoembolization (TACE) and 10 mg arsenic trioxide by intravenous infusion for 5 hours per day, 3 days after TACE. Each cycle consisted of 14 days' administration, and repeated after 2 weeks. Each patient was received 3-4 successive cycles. Group B was received periodic TACE alone. OBJECTIVE: efficiency, benefit rate, quality of life and the correlates with metastatic tumor size and number in the both groups were recorded. RESULTS: The objective efficiency was 26.7% (8/30), and the benefit rate was 60.0% (18/30) in group A, while they were 0 and 16.7% (5/30) in group B with significant statistics differences (χ(2) = 7.067, P = 0.008; χ(2) = 11.915, P = 0.001). The quality of life was improved in 4 patients and stable in 18 of group A, while no patient was improved and 13 were stable in group B (χ(2) = 9.669, P = 0.008). There was a significantly positive correlation between the tumor burden and therapeutic effect (Kendall r = -0.765, P < 0.001; Spearman r = -0.821, P < 0.001). CONCLUSION: Arsenic trioxide combined TACE is an effective treatment method in treating primary liver cancer with pulmonary metastases.