DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.
1 July 2023 in Journal of Hepatocellular Carcinoma
Purpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC. Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts. Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5– 97.0) and 75.4% (95% CI 53.6– 85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5– 97.1) and 79.2% (95% CI 63.6– 90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47– 2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89– 10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0– 14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66– 2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group. Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.
24 November 2015 in CardioVascular and Interventional Radiology
To further evaluate the efficacy and safety of computed tomography (CT)-guided iodine 125 (125I) brachytherapy to treat locally advanced non-small cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). This study obtained written consent from all patients and was approved by our institution. From January 2006 to June 2018, 210 NSCLC patients (progression of first-line CCRT) were retrospectively recruited and then divided into two groups. A total of 116 patients were given CT-guided 125I brachytherapy and second-line chemotherapy (group A), and 94 were treated with second-line chemotherapy alone (group B). In group A, local response rate (LRR) within 3 years was significantly better (P<0.05). Mean survival time [progression-free survival time (PFST) and overall survival (OS)] was 15.1±1.4 months and 21.2±1.6 months in group A compared with 10.0±1.4 months and 16.2±1.7 months in group B (PFST: P<0.01, HR=1.472, 95% CI 1.097–1.975; OS: P = 0.036, HR=1.342, 95% CI 1.005–1.791). Tumor size and No. of first cycle chemotherapy were independent factors that affected survival, ≤3cm largest tumor diameter and more than 4 first cycles of chemotherapy showed longer PFST and OS (P<0.05). Tumor-related clinical symptoms were relieved in group A (P<0.01). No serious complications occurred in the two groups. 125I brachytherapy is effective and safe in locally advanced NSCLC after progression of CCRT.
Percutaneous transhepatic biliary drainage (PTBD) does not always lead to a reduction in serum total bilirubin (TBil) level in patients with hepatocellular carcinoma and obstructive jaundice. We aimed to develop a model for pre-PTBD prediction of post-procedural TBil decrease in these patients. Retrospective database searches were conducted at four teaching hospitals (reference period: January 2010 to December 2018), and baseline characteristics of eligible patients were extracted. Any decrease in TBil after PTBD and the lowest level of TBil post-PTBD <5 mg/dL, 3 mg/dL, and 2 mg/dL were each taken as the standard of effectiveness for computation of its own predictive nomogram. For data dimension decrease and feature selection, the least absolute shrinkage and selection operator (LASSO) regression model was used. A multivariable logistic regression analysis was used to develop nomograms. Each nomogram's performance was internally evaluated for its calibration, discriminative ability, and clinical usefulness. Included in the study were 138 patients. The model for end-stage liver disease (MELD) score, platelet count, and portal vein thrombosis (PVT) were predictors in the nomogram for any decrease in TBil; international normalized ratio (INR), MELD score, platelet count, and PVT were predictors for a decrease to <5 mg/dL; MELD score, cholinesterase level (CHE), platelet count, and PVT were predictors for a decrease to <3 mg/dL; and MELD score, CHE, platelet count, and pre-albumin level were predictors for a decrease to <2 mg/dL. The clinical value of the nomograms was proven by decision curve analysis. These models may help inform clinical decision making for performing PTBD procedures.