A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer

IntroductionThis study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped.MethodsOPSCC patients (n = 122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan–Meier plots (log-rank test). Cox proportional hazard model was used to calculate hazard ratios (HR).ResultsThe overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV⁺ tumours had a better 5-years overall survival (78% vs. 46%, p = 0.001) and a better 5-years disease specific survival (90% vs. 70%, p = 0.016) compared to patients with HPV⁻ tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR = 3.89, p = 0.005), advanced T-stage (HR = 1.81, p = 0.050), advanced N-stage (HR = 5.86, p = 0.001) and >10 pack-years of smoking (HR = 3.45, p = 0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR = 0.40, p = 0.031).ConclusionsOur results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC.     

Head and neck squamous cell carcinomas among males of the three largest Asian diasporas in the US, 2004–2013

BackgroundHead and neck squamous cell carcinomas (HNSCC) have not been fully examined in the Asian diasporas in the US, despite certain Asian countries having the highest incidence of specific HNSCCs.MethodsNational Cancer Database was used to compare 1046 Chinese, 887 South Asian (Indian/Pakistani), and 499 Filipino males to 156,927 Non-Hispanic White (NHW) males diagnosed with HNSCC between 2004−2013. Multinomial logistic regression was used to assess the association of race/ethnicity with two outcomes – site group and late-stage diagnosis. Temporal trends were explored for site groups and subsites.ResultsSouth Asians had a greater proportion of oral cavity cancer [OCC] compared to NHWs (59 % vs. 25 %; OR_adj =7.3 (95 % CI: 5.9–9.0)). In contrast, Chinese (64 % vs. 9%; OR_adj =34.0 (95 % CI: 26.5–43.6)) and Filipinos (47 % vs. 9%; OR_adj =10.0 (95 % CI: 7.8–12.9)) had a greater proportion of non-oropharyngeal cancer compared to NHWs. All three Asian subgroups had a higher likelihood of being diagnosed by age 40 (14 % Chinese, 10 % South Asian and 8% Filipino compared to 3% in NHW; p < 0.001). Chinese males had lower odds of late-stage diagnosis, compared to NHWs. South Asian cases doubled from 2004 to 2013 largely due to an increase in OCC cases (34 cases in 2004 to 86 in 2013).ConclusionAsian diasporas are at a higher likelihood of specific HNSCCs. Risk factors, screening and survival need to be studied further, and policy changes are needed to promote screening and to discourage high-risk habits in these Asian subgroups.     

Coordinate Mapping of Hyolaryngeal Mechanics in Swallowing

Characterizing hyolaryngeal movement is important to dysphagia research. Prior methods require multiple measurements to obtain one kinematic measurement whereas coordinate mapping of hyolaryngeal mechanics using Modified Barium Swallow (MBS) uses one set of coordinates to calculate multiple variables of interest. For demonstration purposes, ten kinematic measurements were generated from one set of coordinates to determine differences in swallowing two different bolus types. Calculations of hyoid excursion against the vertebrae and mandible are correlated to determine the importance of axes of reference.To demonstrate coordinate mapping methodology, 40 MBS studies were randomly selected from a dataset of healthy normal subjects with no known swallowing impairment. A 5 ml thin-liquid bolus and a 5 ml pudding swallows were measured from each subject. Nine coordinates, mapping the cranial base, mandible, vertebrae and elements of the hyolaryngeal complex, were recorded at the frames of minimum and maximum hyolaryngeal excursion. Coordinates were mathematically converted into ten variables of hyolaryngeal mechanics.Inter-rater reliability was evaluated by Intraclass correlation coefficients (ICC). Two-tailed t-tests were used to evaluate differences in kinematics by bolus viscosity. Hyoid excursion measurements against different axes of reference were correlated. Inter-rater reliability among six raters for the 18 coordinates ranged from ICC = 0.90 - 0.97. A slate of ten kinematic measurements was compared by subject between the six raters. One outlier was rejected, and the mean of the remaining reliability scores was ICC = 0.91, 0.84 - 0.96, 95% CI. Two-tailed t-tests with Bonferroni corrections comparing ten kinematic variables (5 ml thin-liquid vs. 5 ml pudding swallows) showed statistically significant differences in hyoid excursion, superior laryngeal movement, and pharyngeal shortening (p < 0.005). Pearson correlations of hyoid excursion measurements from two different axes of reference were: r = 0.62, r² = 0.38, (thin-liquid); r = 0.52, r² = 0.27, (pudding).Obtaining landmark coordinates is a reliable method to generate multiple kinematic variables from video fluoroscopic images useful in dysphagia research.     

The physical basis of reflective communication between fish,with special reference to the horse mackerel,Trachurus trachurus

Some properties of reflecting structures in the external surfaces of Trachurus trachurus and some other fish are described. These are related to the hypothesis that such structures are useful, especially to schooling fish, for communicating information on relative positions, orientations, and movements between neighbours. In addition to the silvery layers on the main body surfaces, there are: (a) highly silvered patches on the tail, the pectoral fins and the jaws which, in the sea, will become much brighter or darker with any movement such as a tailbeat or mouth opening which changes their orientations in the ambient lightfield, and (b) structures such as the dorsal lateral line which, in the sea, will only appear bright from certain directions. To us, the colours of the ventral flanks change from bright red to blue with direction orientations and have special reflectivity curves close to those predicted by A.F. Huxley for interference reflectors which are ''ideal'' λ/4 stacks of guanine crystals and cytoplasm. The wavebands best reflected by such platelets move to shorter wavelengths with increasing angle of incidence, also in accord with these equations. At normal incidence, the outer layer of platelets reflects maximally for far-red light which penetrates only a short distance in the sea. Such layers can, however, be useful at oblique angles where they reflect maximally in the yellow and blue. The inner layer of reflectors reflects very strongly in the blue at normal incidence, but reflects in the ultra-violet at oblique angles. Some theoretical studies are made on the ways in which the patterns of reflectivity by single and superposed layers of λ/4 stacks could signal a fish''s movements or its position relative to its neighbours.     

Improving diagnostic strategies for ovarian cancer in Filipino women using ultrasound imaging and a multivariate index assay

ObjectiveTo evaluate the clinical performance and overall utility of imaging and biomarker assays in discriminating between benign and malignant ovarian masses in a Filipino population.MethodsThis is a prospective cohort study among Filipino women undergoing assessment for an ovarian mass in a tertiary center. All included patients underwent a physical examination before level III specialist ultrasonographic and Doppler evaluation, multivariate index assay (MIA2G), and surgery for an adnexal mass. Ovarian tumors were classified as high-risk for malignancy based on the International Ovarian Tumour Analysis (IOTA) – Logistic Regression 2 (LR2) score. The ovarian imaging and biomarker results were correlated with the reference standard: histological findings.ResultsAmong the 379 women with adnexal masses enrolled in this study, 291 were evaluable with ultrasound imaging, biomarker assays, and histopathological results. The risk of malignancy was higher for women classified as high-risk based on IOTA-LR2 (≥10%). The sensitivity, specificity, and diagnostic accuracy for the prediction of malignancy were 81.2%, 81%, and 0.81 (95% CI: 0.77–0.86) for IOTA-LR2; 77.5%, 66.7%, and 0.72 (95% CI: 0.67–0.77) for CA-125; and 91.3%, 41.2%, and 0.66 (95% CI: 0.62–0.71) for MIA2G. A combination of IOTA-LR2 and MIA2G significantly influenced the diagnostic performance and the result. When MIA2G was combined with IOTA-LR2 in parallel, the sensitivity (94.2%) and NPV (87.7%) increased, but the specificity (37.3%) decreased. When combined with IOTA-LR2 in series, there were fewer false positives, which resulted in improved specificity (85%).ConclusionThis study determined the utility of ovarian imaging and a second-generation multivariate index assay in predicting the risk of ovarian malignancy. IOTA-LR2 and MIA2G were useful in classifying patients with a high risk for ovarian malignancy.