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Texture analysis of intermediate-advanced hepatocellular carcinoma: prognosis and patients' selection of transcatheter arterial chemoembolization and sorafenib.

ABSTRACT: Transcatheter arterial chemoembolization (TACE) and sorafenib combination treatment for unselected hepatocellular carcinoma (HCC) is controversial. We explored the potential of texture analysis for appropriate patient selection. There were 261 HCCs included (TACE group: n = 197; TACE plus sorafenib (TACE+Sorafenib) group n = 64). We applied a Gabor filter and wavelet transform with 3 band-width responses (filter 0, 1.0, and 1.5) to portal-phase computed tomography (CT) images of the TACE group. Twenty-one textural parameters per filter were extracted from the region of interests delineated around tumor outline. After testing survival correlations, the TACE group was subdivided according to parameter thresholds in receiver operating characteristic curves and compared to TACE+Sorafenib group survival. The Gabor-1-90 (filter 0) was most significantly correlated with TTP. The TACE group was accordingly divided into the TACE-1 (Gabor-1-90 ≤ 3.6190) and TACE-2 (Gabor-1-90 > 3.6190) subgroups; TTP was similar in the TACE-1 subgroup and TACE+Sorafenib group, but shorter in the TACE-2 subgroup. Only wavelet-3-D (filter 1.0) correlated with overall survival (OS), and was used for subgrouping. The TACE-5 (wavelet-3-D ≤ 12.2620) subgroup and the TACE+Sorafenib group showed similar OS, while the TACE-6 (wavelet-3-D > 12.2620) subgroup had shorter OS. Gabor-1-90 and wavelet-3-D were consistent.Independent of tumor number or size, CT textural parameters are correlated with TTP and OS. Patients with lower Gabor-1-90 (filter 0) and wavelet-3-D (filter 1.0) should be treated with TACE and sorafenib. Texture analysis holds promise for appropriate selection of HCCs for this combination therapy.

SUBMITTER: Fu S

PROVIDER: S-EPMC5514956 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Targeted therapy is currently the standard treatment for advanced hepatocellular carcinoma (HCC), but an effective treatment after the discontinuation of sorafenib therapy remains uncertain. We aim to investigate the survival benefits of transcatheter arterial chemoembolization (TACE) after stopping sorafenib therapy. We retrospectively analyzed all patients with advanced HCC, who had received palliative TACE after terminating sorafenib therapy, from January 2008 to June 2016. Patients who were in the terminal stage (Child-Pugh class C or performance status 3-4), who received a liver transplantation, or who had received any HCC treatment other than TACE, were excluded. Finally, 28 patients were recruited as the TACE group, and were randomly matched 1:1 by age, gender, Child-Pugh class, extrahepatic metastasis, and portal vein thrombosis with 28 controls who only received supportive care. For avoiding any immortal time bias, the index date of outcome follow-up was also matched. Cumulative incidences of, and hazard ratios (HRs) for, patient mortality were analyzed. The baseline demographic data between the TACE group and the control group were similar, but the 1-year overall survival rate in the TACE group was significantly higher than that of the control group (41.2%, 95% confidence interval [CI]: 19.4-63.0% vs. 24.5%, 95% CI: 6.3-42.7%; p < 0.01). In multivariate analysis, after adjusting for alpha-fetoprotein > 400ng/mL, Child-Pugh class B, and tumor extension > 50% of liver volume, TACE was independently associated with a decreased mortality risk(HR 0.19, 95% CI: 0.08-0.42). In addition, tumor extension > 50% of the liver was another independent prognostic factor associated with an increased mortality risk (HR 2.99, 95% CI: 1.31-6.82). Multivariate stratified analyses verified the association of TACE with a decreased mortality rate in each patient subgroup (all HR < 1.0). By controlling intrahepatic tumor growth, TACE may be a treatment option for use in improving patient survival in advanced HCC, after the termination of sorafenib therapy.

Project description:BackgroundPatients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC.MethodsGenes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined.ResultsThe detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells.ConclusionThe response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.

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Texture analysis of intermediate-advanced hepatocellular carcinoma: prognosis and patients' selection of transcatheter arterial chemoembolization and sorafenib.

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