Association of homozygous variants of STING1 with outcome in human cervical cancer
CANCER SCIENCE
Authors: Lubbers, Joyce M.; Koopman, Bart; de Klerk-Sluis, Jessica M.; van Rooij, Nienke; Plat, Annechien; Pijper, Harry; Koopman, Timco; van Hemel, Bettien M.; Hollema, Harry; Wisman, Bea; Nijman, Hans W.; de Bruyn, Marco
Abstract
DNA-sensing receptor Cyclic GMP-AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS-STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING-encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy. To start to address this, we defined the genetic landscapes of STING1 in cervical scrapings and investigated their corresponding clinical characteristics across a unique cohort of cervical cancer patients and compared them with independent control cohorts. Although we did not observe an enrichment of particular STING1 allelic variants in cervical cancer patients, we did find that the occurrence of homozygous variants HAQ/HAQ and R232H/R232H of STING1 were associated with both younger age of diagnosis and higher recurrence rate. These findings were accompanied by worse survival, despite comparable mRNA and protein levels of STING and numbers of infiltrated CD8(+) T cells. Our findings suggest that patients with HAQ/HAQ and R232H/R232H genotypes may have a dysfunctional cGAS-STING pathway that fails to promote efficient anticancer immunity. Interestingly, the occurrence of these genotypes coincided with homozygous presence of the V48V variant, which was found to be individually associated with worse outcome. Therefore, we propose V48V to be further evaluated as a novel prognostic marker for cervical cancer.
Hypertension in the Young Adult Trauma Population: Rethinking the Traditional "Incidentaloma"
JOURNAL OF SURGICAL RESEARCH
Authors: Tremont, Jaclyn N. Portelli; Orleans, Brian; Strassle, Paula D.; Dreesen, Elizabeth B.; Brownstein, Michelle R.
Abstract
Background: Hypertension (HTN) is a treatable and preventable risk factor for cardiovascular disease that is often overlooked in young adults. As a result, young patients with HTN may enter the health care system as a trauma without a preexisting diagnosis. The potential impact of HTN (diagnosed and undiagnosed) on trauma outcomes is not known. Materials and methods: Patients aged 18-39 y from the 2013-2017 North Carolina Trauma Registry were included. Patients were stratified as having no HTN, previously diagnosed HTN (PD-HTN), or newly diagnosed HTN (ND-HTN) during a trauma admission. Multivariable logistic and linear regression compared inpatient outcomes between patients with and without HTN, as well as ND-HTN and PD-HTN. Results: Six percent of trauma patients were diagnosed with HTN (n = 1906; 14% ND-HTN). Those with HTN were more likely to have an inpatient complication (odds ratio [OR]: 1.65, 95% confidence interval [CI]: 1.32-2.07) and intensive care unit stay (OR: 1.28, 95% CI: 1.12-1.46) compared with patients without HTN. Compared with PD-HTN, those with ND-HTN were more likely to present with extreme injury. In addition, patients with ND-HTN had higher odds of inpatient complications (OR: 1.95, 95% CI: 1.18-3.22) and 30-d readmission (OR: 2.00, 95% CI: 0.95-4.20) after accounting for demographics and injury severity. Conclusions: More than 10% of young adult trauma patients with HTN are not diagnosed before admission. HTN appears to have a detrimental impact on patient outcomes, with newly diagnosed patients having the worst outcomes. Trauma may serve as an opportunity for the diagnosis and treatment of HTN in young adults. Future studies should assess the impact of intervention on trauma outcomes. (C) 2020 Elsevier Inc. All rights reserved.