Erratum: Exploring APOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer.

[This corrects the article DOI: 10.1016/j.isci.2022.105077.].

Exploring ABOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer.

APOBEC3 family members are cytidine deaminases catalyzing conversion of cytidine to uracil. Many studies have established a link between APOBEC3 expression and cancer development and progression, especially APOBEC3A (A3A) and APOBEC3B (A3B). Preclinical studies with human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) and clinical trial specimens revealed induction of A3B, but not A3A expression after demethylation. We examined the kinetic features of the cytidine deaminase activity for full length A3B and found that longer substrates and a purine at -2 position favored by A3B, whereas A3A prefers shorter substrates and an adenine or thymine at -2 position. The importance and biological significance of A3B catalytic activity rather than A3A and a preference for purine at the -2 position was also established in HPV+ HNSCCs. Our study explored factors influencing formation of A3A and A3B-related cancer mutations that are essential for understanding APOBEC3-related carcinogenesis and facilitating drug discovery.

Systemic Inflammation is Associated with Cardiometabolic Risk Factors and Clinical Outcomes.

Purpose: Assessing an individual's systemic inflammatory state is vital to understand inflammation's role in cardiometabolic diseases and identify those at the greatest risk of disease. We generated global inflammation scores and investigated their associations with cardiometabolic risk factors and adverse outcomes. Patients and Methods: Aggregate Inflammation Scores (AIS) and Principal Component Analysis (PCA) scores were generated for 7287 Framingham Heart Study participants using up to 26 inflammation-related proteins, with higher scores reflecting a pro-inflammatory milieu. Multivariable regression and proportional hazards analyses were conducted to investigate the associations of inflammation with cardiometabolic risk factors and outcomes. The primary outcomes for cross-sectional analyses included age, cigarette smoking, fasting lipid and glucose levels, blood pressure, body mass index (BMI), and hypertension, diabetes, and obesity. For prospective analyses, new-onset hypertension, diabetes, obesity, cardiovascular disease and all-cause mortality were investigated. Results: Higher inflammation scores were associated with smoking and older age, higher BMI, systolic blood pressure, lipids, and glucose levels, and with greater odds of hypertension and diabetes after adjusting for age, sex, cohort, and BMI (all p < 0.001). Higher baseline scores were associated with greater odds of new-onset hypertension after adjusting for traditional risk factors (OR [95% CI] per one standard deviation [1-SD] increase, AIS: 1.33 [1.21-1.47], PCA score: 1.26 [1.12-1.42], p < 0.001). The AIS also was associated with new-onset diabetes (1.32 [1.14-1.52], p < 0.001). Proportional hazards analyses revealed greater risk of new-onset cardiovascular disease events and all-cause mortality (HR [95% CI] per 1-SD, AIS: 1.25 [1.14-1.37] and 1.32 [1.23-1.42], PCA score: 1.22 [1.13-1.33] and 1.40 [1.31-1.49], p < 0.001). Conclusion: Global inflammation scores encompassing an array of pro- and anti-inflammatory proteins and pathways may enhance risk assessment for cardiometabolic diseases. The AIS and PCA scores provide further opportunities to investigate the mechanisms of inflammation-related risk of disease.