ABSTRACT
BACKGROUND: Cellular senescence, a state of stable growth arrest, is intertwined with human cancers. However, characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma (HCC) remains unexplored. AIM: To address this issue, we delineated cellular senescence landscape across HCC. METHODS: We enrolled two HCC datasets, TCGA-LIHC and International Cancer Genome Consortium (ICGC). Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes. Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system. TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry, immunoblotting and quantitative real-time polymerase chain reaction. The influence of TMF-regulated nuclear protein (TRNP)1 on HCC senescence and growth was proven via a series of experiments. RESULTS: TCGA-LIHC patients were classified as three cellular senescence subtypes, named C1-3. The robustness and reproducibility of these subtypes were proven in the ICGC cohort. C2 had the worst overall survival, C1 the next, and C3 the best. C2 presented the highest levels of immune checkpoints, abundance of immune cells, and immunogenetic indicators. Thus, C2 might possibly respond to immunotherapy. C2 had the lowest somatic mutation rate, while C1 presented the highest copy number variations. A cellular senescence-relevant gene signature was generated, which can predict patient survival, and chemo- or immunotherapeutic response. Experimentally, it was proven that TRNP1 presented the remarkable upregulation in HCCs. TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth. CONCLUSION: These findings provide a systematic framework for assessing cellular senescence in HCC, which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.
ABSTRACT
Objective: Infectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China. Methods: A total of 9,749 adolescents and young adults aged 15-24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views. Findings: The prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (ß = 0.025, p < 0.05), those without quarantine experience (ß = 0.035, p < 0.001), those with lower educational level (p < 0.001), those with lower family income (p < 0.01), and those with higher PTSD symptoms (ß = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income (p < 0.01), depression symptoms (ß = 0.056, p < 0.001), anxiety symptoms (ß = 0.051, p < 0.001), and mental health problems (ß = 0.027, p < 0.05). Conclusion: The stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions.
