Circulating Cell-Free SEPT9 DNA Methylation in Blood Is a Biomarker for Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma Patients.

BACKGROUND: Tumorous SEPT9 (septin 9, SEPTIN9) circulating cell-free DNA (ccfDNA) methylation in blood plasma is a powerful biomarker for diagnosis, molecular staging, prognosis, and recurrence monitoring in head and neck squamous cell carcinoma (HNSCC) patients. The present study aimed to evaluate the clinical performance of SEPT9 ccfDNA methylation to detect post-surgical minimal residual disease (MRD) in patients with localized or locally advanced HNSCC treated with curative intent. METHODS: We applied quasi-digital methylation-specific real-time PCR to quantify SEPT9 ccfDNA methylation levels 2 to 30 days post-surgically in plasma from n = 219 prospectively enrolled HNSCC patients. We tested the associations of SEPT9 ccfDNA methylation with clinicopathological parameters and used Kaplan-Meier and Cox proportional hazards analyses for univariate, pairwise bivariate, and multivariate analyses of disease-free survival. RESULTS: Of 219 patients, 26.5% (58/219) were post-surgically SEPT9 ccfDNA methylation positive. SEPT9 ccfDNA methylation positivity was significantly associated with tumor site, American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC; 8th edition) tumor stage, nodal category and extracapsular extension, lymphatic and vascular invasion, and surgical margin. Bivariate Cox proportional hazards analysis proved post-surgical SEPT9 ccfDNA methylation positivity to be an independent prognostic factor tested together with AJCC/UICC tumor stage (SEPT9: hazard ratio [HR] = 2.43, 95% CI, 1.37-4.30, P = 0.002; AJCC/UICC stage: HR = 1.48, 95% CI, 1.11-1.98, P = 0.008). CONCLUSIONS: Post-surgical SEPT9 ccfDNA methylation may aid to identify high-risk HNSCC patients who could benefit from an intensified adjuvant treatment and surveillance.

Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools.

BACKGROUND: Our study describes the neoexpression (Juno) and suppression (catsperD, dysferlin, Fer1L5 and otoferlin) of selected genes in oral squamous cell carcinomas (OSCCs). As the expression pattern of these genes allows a "yes" or "no" statement by exhibiting an inverse expression pattern in malignant versus benign tissues, they represent potential biomarkers for the characterization of oral malignancies, particularly OSCCs. METHODS: Differential expression analyses of selected genes of interest were examined by quantitative PCR of oral cancer tissues compared to normal. RESULTS: Five candidates out of initially nine genes were examined, demonstrating Juno as a putative new tumor marker selectively expressed in OSCCs. Interestingly, the expression of four other genes in benign tissues was completely repressed in tumor tissues with a specificity and sensitivity of 100%. No correlation was observed regarding patients' sex, tumor staging and grading, and tumor site. CONCLUSION: The present study shows novel candidates that might be useful tools for oral cancer diagnosis. The neoexpression of Juno in cancerous tissues makes it a promising target molecule regarding its potential in diagnosis as well a therapeutic tool. Moreover, our observations suggest that also the repression of gene expression can be used for diagnosing-at least-OSCCs.

Direct Comparison of the Edwards Intuity Elite and Sorin Perceval S Rapid Deployment Aortic Valves.

BACKGROUND: Rapid deployment aortic valve replacement (RDAVR) has emerged as an attractive alternative to conventional aortic valve replacement. This single-center study directly compared two commercially available rapid deployment valves with regard to clinical outcomes, valve-related complications, and hemodynamic performance. METHODS: A total of consecutive 156 patients underwent RDAVR with the Intuity Elite (Edwards Lifesciences, Irvine, CA [Intuity group, n = 117] or the Perceval S (Sorin Group Italia Srl, Saluggia, Italy [Perceval group, n = 39]) between September 2012 and March 2016 at our institution. Perioperative data, including 30-day all-cause mortality, and echocardiographic measurements were assessed and retrospectively analyzed from our institutional database. RESULTS: Preoperative variables, including mean age (77 ± 5 years), European System for Cardiac Operative Risk Evaluation (6.8 ± 2.1), and body mass index (27 ± 5 kg/m2), did not differ between groups. More male patients (60% versus 15%) with a higher body surface area (1.9 ± 0.2 m2 versus 1.7 ± 0.2 m2) and body weight (78 ± 13 kg versus 71 ± 15 kg) were in the Intuity group compared with the Perceval group, respectively (p < 0.05). Implanted RDAVR size (23.3 ± 1.8 mm versus 23.4 ± 1.5 mm), concomitant coronary artery bypass graft surgery (48% versus 33%), number of grafts, cardiopulmonary bypass, and aortic clamp time were comparable between the Intuity group and the Perceval group. Thirty-day mortality (Intuity 2.6% versus Perceval 5.1%) and valve-related complications (Intuity 12.0% versus Perceval 20.5%), including postoperative pacemaker implantation (Intuity 8.5% versus Perceval 12.8%), did not differ between groups. At discharge echocardiography, indexed effective orifice area was higher in the Intuity group, but peak or mean pressure gradients were comparable between groups. CONCLUSIONS: Performing RDAVR with the Intuity and Perceval rapid deployment valves provides comparable good clinical outcomes and valve hemodynamics, with low valve-related complication rates. The rate of pacemaker implantation was comparable for both rapid deployment valves, ranging from 8% to 13%.