Background: Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation can affect tumor heterogeneity by participating in gene expression. Methods: In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. Results: 965 potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites’ information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. Conclutions: Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.

Objective: Resilience instruments specific to family caregivers (FCs) in cancer are limited. This study was designed to validate the 10-item Resilience Scale Specific to Cancer (RS-SC-10) in FCs using multidimensional item response theory (MIRT) analysis.Methods: 382 FCs were enrolled from Be Resilient to Cancer Program (BRCP) and administered with RS-SC-10 and 36-item Short Form Health Survey (SF-36). MIRT was performed to evaluate item parameters while Generalized Additive Model (GAM) and Latent Profile Analysis (LPA) were performed to test the non-linear relationship between resilience (RS-SC-10) and Quality of Life (QoL, SF-36).Results: RS-SC-10 retained 10 items with high multidimensional discrimination, monotonous thresholds and its original two-factor structure (Generic and Shift-Persist). Four latent resilience subgroups were identified and a non-linear dose-response pattern between resilience and QoL was confirmed (per-SD increase OR= 1.62, 95%CI, 1.16-2.13, p=0.0019).Conclusion: RS-SC-10 is a brief and suitable resilience instrument for FCs in cancer. The resilience screening of patients and FCs can be performed simultaneously in clinical practice.

Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC.Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004, hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

Background: The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25).Methods: From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs.Results: 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r= 0.38-0.44, all p<0.001). Linear regression estimated +8.9 and -6.7 as the MCIDs of RS-SC-25, and +3.4 and -2.5 for RS-SC-10. Distribution-based methods estimated +9.9 and -9.9 as the MCIDs of RS-SC-25, and +4.0 and -4.0 for RS-SC-10. ROC estimated +5.5 and -4.5 as the MCIDs of RS-SC-25, and +2.0 and -1.5 for RS-SC-10.Conclusions: The most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.

The cross talk between Epstein-Barr virus (EBV) and the host cell transcriptome assumes important roles in the oncogenesis of EBV-associated malignancies. Here, we first observed that endogenous Gal-9 expression was persistently increased along with an overturned V-type change in antivirus signaling during the immortalization of EBV-transformed B cells.