Differences in biomarker expression in HNSCC according to p53 status.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5523-5523 ◽  
Author(s):  
Rebecca Anne Feldman-Moreno ◽  
Ariane C. Kemkes ◽  
Joanne Xiu ◽  
Richard Blevins ◽  
Paula Esmay ◽  
...  

5523 Background: Patients with p53 wildtype head and neck squamous cell carcinoma (HNSCC) tend to be HPV-positive, which associates with better prognosis. The purpose of this study was to explore biomarker expression profiles for insight into molecular differences in HNSCC patients based on p53 status. Methods: TP53 gene sequencing using the AmpliChip p53 microarray (Roche Molecular Systems, Inc.) was attempted on 61 HNSCC patients previously tested with Caris Target Now tumor profiling service. DNA was extracted from a FFPE sample, amplified and processed on the AmpliChip p53 microarray to detect single base pair substitution and deletion mutations in exons 2 - 11 and their flanking splice sites in the TP53 gene (GenBank X54156). EGFR FISH , HER2 IHC and 22 other predictive biomarkers, e.g. TS, TOPO2A, MGMT, etc., were assayed and retrospectively analyzed. All tests were performed in a CLIA-certified lab and interpreted by board-certified pathologists or cytogeneticists. Statistical analysis was performed using SPSS (PASW statistics17) for parametric and non-parametric tests of independence. Results: 52 cases provided sufficient quality DNA for p53 analysis and results revealed a mutation rate of 25% in HNSCC patients. Interestingly, only EGFR FISH and HER2 IHC (p=.002 and p=.004, respectively) were differentially expressed in wildtype vs. mutated p53. Matched-pair analysis in the p53 mutated subgroup (n=13) showed no significant trend regarding EGFR status (p=.763) but a slight trend towards HER-2 negativity (p=.020). In the p53 wildtype subgroup (n=39), a strong association with EGFR FISH non-amplification (n=28, 71.8%, p<.001) as well as HER-2 negativity (n=38, 97.4%, p<.001) was shown. Conclusions: To our knowledge, this is the first analysis of differential biomarker expression profiles in HNSCC based on p53 status. We hypothesize that the absence of EGFR amplification in the p53 wildtype cancers may be a contributing factor to the improved prognosis observed in HPV-positive HNSCC. Additionally, the strong association between p53 wildtype HNSCC patients and EGFR non-amplification suggests EGFR-targeted therapies like cetuximab would likely fail in p53 wildtype patients.

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 155
Author(s):  
Yuchen Zhang ◽  
Lina Zhu ◽  
Xin Wang

Pancreatic ductal adenocarcinoma (PDAC), the predominant subtype of pancreatic cancer, has been reported with equal mortality and incidence for decades. The lethality of PDAC is largely due to its late presentation, when surgical resection is no longer an option. Similar to other major malignancies, it is now clear that PDAC is not a single disease, posing a great challenge to precise selection of patients for optimized adjuvant therapy. A representative study found that PDAC comprises four distinct molecular subtypes: squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX). However, little is known about the molecular mechanisms underlying specific PDAC subtypes, hampering the design of novel targeted agents. In this study we performed network inference that integrates miRNA expression and gene expression profiles to dissect the miRNA regulatory mechanism specific to the most aggressive squamous subtype of PDAC. Master regulatory analysis revealed that the particular subtype of PDAC is predominantly influenced by miR-29c and miR-192. Further integrative analysis found miR-29c target genes LOXL2, ADAM12 and SERPINH1, which all showed strong association with prognosis. Furthermore, we have preliminarily revealed that the PDAC cell lines with high expression of these miRNA target genes showed significantly lower sensitivities to multiple anti-tumor drugs. Together, our integrative analysis elucidated the squamous subtype-specific regulatory mechanism, and identified master regulatory miRNAs and their downstream genes, which are potential prognostic and predictive biomarkers.


Author(s):  
Darius M. Thiesen ◽  
Dimitris Ntalos ◽  
Alexander Korthaus ◽  
Andreas Petersik ◽  
Karl-Heinz Frosch ◽  
...  

Abstract Introduction For successful intramedullary implant placement at the femur, such as nailing in unstable proximal femur fractures, the use of an implant that at least reaches or exceeds the femoral isthmus and yields sufficient thickness is recommended. A number of complications after intramedullary femoral nailing have been reported, particularly in Asians. To understand the anatomical features of the proximal femur and their ethnic differences, we aimed to accurately calculate the femoral isthmus dimensions and proximal distance of Asians and Caucasians. Methods In total, 1189 Asian and Caucasian segmented 3D CT data sets of femurs were analyzed. The individual femoral isthmus diameter was precisely computed to investigate whether gender, femur length, age, ethnicity or body mass index have an influence on isthmus diameters. Results The mean isthmus diameter of all femurs was 10.71 ± 2.2 mm. A significantly larger diameter was found in Asians when compared to Caucasians (p < 0.001). Age was a strong predictor of the isthmus diameter variability in females (p < 0.001, adjusted r2 = 0.299). With every year of life, the isthmus showed a widening of 0.08 mm in women. A Matched Pair Analysis of 150 female femurs showed a significant difference between isthmus diameter in Asian and Caucasian femurs (p = 0.05). In 50% of the cases the isthmus was found in a range of 2.4 cm between 16.9 and 19.3 cm distal to the tip of the greater trochanter. The female Asian femur differs from Caucasians as it is wider at the isthmus. Conclusions In absolute values, the proximal isthmus distance did not show much variation but is more proximal in Asians. The detailed data presented may be helpful in the development of future implant designs. The length and thickness of future standard implants may be considered based on the findings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long H. Ngo ◽  
M. Austin Argentieri ◽  
Simon T. Dillon ◽  
Blake Victor Kent ◽  
Alka M. Kanaya ◽  
...  

AbstractBlood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Roman Rüdiger ◽  
Franziska Geiser ◽  
Manuel Ritter ◽  
Peter Brossart ◽  
Mignon-Denise Keyver-Paik ◽  
...  

Abstract Background Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. Methods Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002–December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). Results Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar’s test, P = 0.346) between both collectives. Conclusion Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.


2020 ◽  
Vol 18 (1) ◽  
pp. 43-73
Author(s):  
Lars Osterbrink ◽  
Paul Alpar ◽  
Alexander Seher

AbstractReviewing and rating are important features of many social media websites, but they are found on many e-commerce sites too. The combination of social interaction and e-commerce is sometimes referred to as social commerce to indicate that people are supporting each other in the process of buying goods and services. Rgeviews of other consumers have a significant effect on consumer choice because they are usually considered authentic and more trustworthy than information presented by a vendor. The collaborative effort of consumers helps to make the right purchase decision (or prevent from a wrong one). The effect of reviews has often been researched in terms of helpfulness as indicated by their readers. Images are an important factor of helpfulness in reviews of experience goods where personal tastes and use play an important role. We extend this research to search goods where objective characteristics seem to prevail. In addition, we analyze potential interaction with other variables. The empirical study is performed with regression analyses on 3,483 search good reviews from Amazon.com followed by a matched pair analysis of 186 review pairs. We find that images have a significant positive effect on helpfulness of reviews of search goods too. This is especially true in case of short and ambiguous reviews.


2010 ◽  
Vol 9 (2) ◽  
pp. 150
Author(s):  
R. Stein ◽  
A. Schröder ◽  
T. Hagen ◽  
J.W. Thüroff

Sign in / Sign up

Export Citation Format

Share Document