To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

OBJECTIVES: To identify modifiable factors that facilitate discussion of potentially sensitive topics between health care providers and young people at preventive service visits after Patient Protection and Affordable Care Act implementation. METHODS: We used data from a national internet survey of adolescents and young adults (13–26 years old) in the United States. Questionnaire construction was guided by formative research and Fisher’s Information-Motivation-Behavioral Skills model. Those who had seen a regular health care provider in the past 2 years were asked about 11 specific topics recommended by national medical guidelines. Four multivariable regression models were used to identify independent predictors of discussions of (1) tobacco use, (2) drug and/or alcohol use, (3) sexually transmitted infections or HIV, and (4) the number of topics discussed. RESULTS: Fewer than half of young people reported having discussed 10 of 11 topics at their last visit. Predictors were similar across all 4 models. Factors independently associated with health discussions included the following: ever talked with a provider about confidentiality (4/4 models; adjusted odds ratio [aOR] = 1.85–2.00), ever had private time with a provider (1 model; aOR = 1.50), use of health checklist and/or screening questionnaire at last visit (4 models; aOR = 1.78–1.96), and time spent with provider during last visit (4 models). Number of years that young men had seen their regular provider was significant in 1 model. Other independent factors were positive youth attitudes about discussing specific topics (3/3 models) and youth involvement in specific health risk behaviors (3/3 models). CONCLUSIONS: Discussions about potentially sensitive topics between health care providers and young people are associated with modifiable factors of health care delivery, particularly provider explanations of confidentiality, use of screening and/or trigger questionnaires, and amount of time spent with their provider.