Development and Validation of Epigenetic Modification-Related Signals for the Diagnosis and Prognosis of Hepatocellular Carcinoma

BackgroundIncreasing evidence has indicated that abnormal epigenetic factors such as RNA m6A modification, histone modification, DNA methylation, RNA binding proteins and transcription factors are correlated with hepatocarcinogenesis. However, it is unknown how epigenetic modification-associated genes contribute to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we constructed the epigenetic modification-associated models that may enhance the diagnosis and prognosis of HCC.MethodsIn this study, we focused on the clinical value of epigenetic modification-associated genes for HCC. Our gene expression data were collected from TCGA and HCC data sets from the GEO database to ensure the reliability of the data. Their functions were analyzed by bioinformatics methods. We used lasso regression, Support vector machine (SVM), logistic regression and Cox regression to construct the diagnostic and prognostic models. We also constructed a nomogram of the practicability of the above-mentioned prognostic model. The above results were verified in an independent liver cancer data set from the ICGC database and clinical samples. Furthermore, we carried out pan-cancer analysis to verify the specificity of the above model and screened a wide range of drug candidates.ResultsMany epigenetic modification-associated genes were significantly different in HCC and normal liver tissues. The gene signatures showed a good ability to predict the occurrence and survival of HCC patients, as verified by DCA and ROC curve analysis.ConclusionGene signatures based on epigenetic modification-associated genes can be used to identify the occurrence and prognosis of liver cancer

Prognostic significance of integrating total metabolic tumor volume and EGFR mutation status in patients with lung adenocarcinoma

Background The objective of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) derived from baseline 18F-2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), in conjunction with epidermal growth factor receptor (EGFR) mutation status, among patients with lung adenocarcinoma (LUAD). Methods We performed a retrospective analysis on 141 patients with LUAD (74 males, 67 females, median age 67 (range 34–86)) who underwent 18F-FDG PET/CT and had their EGFR mutation status determined. Optimal cutoff points for TMTV were determined using time-dependent receiver operating characteristic curve analysis. The survival difference was compared using Cox regression analysis and Kaplan‒Meier curves. Results The EGFR mutant patients (n = 79, 56.0%) exhibited significantly higher 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those with EGFR wild-type (n = 62, 44.0%), with rates of 74.2% vs 69.2% (P = 0.029) and 86.1% vs 67.7% (P = 0.009), respectively. The optimal cutoff values of TMTV were 36.42 cm3 for PFS and 37.51 cm3 for OS. Patients with high TMTV exhibited significantly inferior 2-year PFS and OS, with rates of 22.4% and 38.1%, respectively, compared to those with low TMTV, who had rates of 85.8% and 95.0% (both P < 0.001). In both the EGFR mutant and wild-type groups, patients exhibiting high TMTV demonstrated significantly inferior 2-year PFS and OS compared to those with low TMTV. In multivariate analysis, EGFR mutation status (hazard ratio, HR, 0.41, 95% confidence interval, CI [0.18–0.94], P = 0.034) and TMTV (HR 8.08, 95% CI [2.34–28.0], P < 0.001) were independent prognostic factors of OS, whereas TMTV was also an independent prognosticator of PFS (HR 2.59, 95% CI [1.30–5.13], P = 0.007). Conclusion Our study demonstrates that the integration of TMTV on baseline 18F-FDG PET/CT with EGFR mutation status improves the accuracy of prognostic evaluation for patients with LUAD

Identification of EGFR mutation status in male patients with non-small-cell lung cancer: role of 18F-FDG PET/CT and serum tumor markers CYFRA21-1 and SCC-Ag

Abstract Background The high incidence of epidermal growth factor receptor (EGFR) mutations is usually found in female patients with lung adenocarcinoma who have never-smoked. However, reports concerning male patients are scarce. Thus, this study aimed to explore a novel approach based on 18F-fluoro-2-deoxy-2-deoxyglucose (18F-FDG) PET/CT and serum tumor markers (STMs) to determine EGFR mutation status in male patients with non-small-cell lung cancer (NSCLC). Methods A total of 121 male patients with NSCLC were analyzed between October 2019 and March 2022. All patients underwent 18F-FDG PET/CT scan before treatment and monitored 8 STMs (cytokeratin 19 fragment [CYFRA21-1], squamous cell carcinoma-related antigen [SCC-Ag], carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], carbohydrate antigen [CA] 50, CA125, CA72-4, and ferritin). A comparison was done between EGFR mutant and wild-type patients in terms of the maximum standardized uptake value of primary tumors (pSUVmax) and 8 STMs. We performed receiver operating characteristic (ROC) curve and multiple logistic regression analyses to determine predictors for EGFR mutation status. Results EGFR mutations were detected in 39 patients (32.2%). Compared with patients with EGFR wild-type, EGFR-mutant patients had lower concentrations of serum CYRFA21-1 (2.65 vs. 4.01, P = 0.002) and SCC-Ag (0.67 vs. 1.05, P = 0.006). No significant differences of CEA, NSE, CA 50, CA125, CA72-4 and ferritin were found between the two groups. The presence of EGFR mutations was significantly associated with low pSUVmax (< 8.75), low serum SCC-Ag (< 0.79 ng/mL) and CYFRA21-1 (< 2.91 ng/mL) concentrations. The area under ROC curve values were 0.679, 0.655, 0.685 and 0.754, respectively, for low CYFRA21-1, SCC-Ag, pSUVmax and the combination of these three factors. Conclusions We demonstrated that low concentrations of CYFRA21-1 and SCC-Ag, as well as low pSUVmax, were associated with EGFR mutations, and that the combination of these factors resulted in a higher differentiation of EGFR mutation status in male patients with NSCLC

ICMJE Disclosures

<p>Supplemental material, FAI753160-ICMJE for Strain Distribution in the Anterior Inferior Tibiofibular Ligament, Posterior Inferior Tibiofibular Ligament, and Interosseous Membrane Using Digital Image Correlation by Daorong Xu, Yibei Wang, Chunyu Jiang, Maoqing Fu, Shiqi Li, Lei Qian, Peidong Sun and Jun Ouyang in Foot & Ankle International</p