Introduction: To determine the stage-specific incidence trend of hepatocellular carcinoma (HCC) among US adults. Methods: The age-adjusted incidence rate was extracted from Surveillance, Epidemiology, and End Results database for localized, regional and distant HCC. Trend analyses were conducted in the overall population and stratified by demographic and sociodemographic variables. The annual percentage change (APC) in 2014-2019 was estimated to determine the stage-specific incidence trend. Results: Although the incidence in localized HCC significantly declined, the incidence for regional and distant HCC plateaued in 2014-2019 (APCs, 4.4% [95% CI, -0.2% to 9.3%] and -0.7% [95% CI, -1.8% to 0.5%], respectively) with age and race/ethnicity disparities. More pronounced increases for regional and distant HCC were observed among the elderly (APCs, 8.4% [95% CI, 4.8% to 12.2%] and 2.2% [95% CI, 1.7% to 2.7%] for regional and distant HCC, respectively), non-Hispanic White individuals (APCs, 4.0% [95% CI, 2.9% to 5.1%] and 1.5% [95% CI, 0.7% to 2.4%] for regional and distant HCC, respectively). Conclusions: Disparities in incidence trends may reflect the inequalities in access to primary health care. More efforts are still in great demand for the vulnerable population.

Introduction: Reliable biomarkers are in need to predict the prognosis of hepatocellular carcinoma (HCC). Whilst recent evidence has established the critical role of copper homeostasis in tumor growth and progression, no previous studies have dealt with the copper-related genes (CRGs) signature with prognostic potential in HCC.Methods: To develop and validate a CRGs prognostic signature for HCC, we retrospectively included 353 and 142 patients as the development and validation cohort, respectively. Copper-related Prognostic Signature (Copper-PSHC) was developed using differentially expressed CRGs with prognostic value. The hazard ratio (HR) and the area under the time-dependent receiver operating characteristic curve (AUC) during 3-year follow-up were utilized to evaluate the performance. Additionally, the Copper-PSHC was combined with age, sex, and cancer stage to construct a Copper-clinical-related Prognostic Signature (Copper-CPSHC), by multivariate Cox regression. We further explored the underlying mechanism of Copper-PSHC by analyzing the somatic mutation, functional enrichment, and tumor microenvironment. Potential drugs for the high-risk group were screened.Results: The Copper-PSHC was constructed with nine CRGs. Patients in the high-risk group demonstrated a significantly reduced overall survival (OS) (adjusted HR, 2.65 [95% CI, 1.83–3.84] and 3.30, [95% CI, 1.27–8.60] in the development and validation cohort, respectively). The Copper-PSHC achieved a 3-year AUC of 0.74 [95% CI, 0.67–0.82] and 0.71 [95% CI, 0.56–0.86] for OS in the development and validation cohort, respectively. Copper-CPSHC yield a 3-year AUC of 0.73 [95% CI, 0.66–0.80] and 0.72 [95% CI, 0.56–0.87] for OS in the development and validation cohort, respectively. Higher tumor mutation burden, downregulated metabolic processes, hypoxia status and infiltrated stroma cells were found for the high-risk group. Six small molecular drugs were screened for the treatment of the high-risk group.Conclusion: Copper-PSHC services as a promising tool to identify HCC with poor prognosis and to improve disease outcomes by providing potential clinical decision support in treatment.