scholarly journals PATH-23. GENOMIC LANDSCAPE OF IDH-MUTANT PRIMARY GLIOBLASTOMAS SHOWS DISTINCT CLINICAL AND MOLECULAR FEATURES AND THAT CDKN2A SHOULD BE SUPPLEMENTED WITH MGMTp AND G-CIMP FOR PRECISE PROGNOSTICATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii169-ii169
Author(s):  
Queenie Hoi-Wing Wong ◽  
Gabriel Chun-Hei Wong ◽  
Aden Ka-Yin Chan ◽  
Wai Sang Poon ◽  
Danny Tat-Ming Chan ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Prognostic Marker ◽  
Clinical Analysis ◽  
Targeted Sequencing ◽  
Independent Prognostic Marker ◽  
Molecular Features ◽  
Cdkn2a Deletion ◽  
Ffpe Tissues ◽  
Secondary Glioblastomas ◽  
Primary Glioblastomas

Abstract There have only been rare studies of IDH-mutant primary glioblastomas (IDH-mutant astrocytoma IV); there were one or two studies on secondary glioblastomas. In a cohort of 70 cases, we conducted clinical analysis, methylation profiling, RNA sequencing, targeted sequencing, and TERTp seqeuncing on available FFPE tissues. Median follow-up was 58.2 months (n= 60). IDH-mutant primary glioblastomas had longer median OS (30.4 months) and median PFS (25.9 months) than IDH-mutant secondary glioblastomas as in the literature or established databases. MGMTp methylated cases had better OS (p= 0.001) and it was an independent prognosticator. We previously showed G-CIMP to be an independent prognostic marker for IDH-mutant glioblastomas (NOA 2019). Although CDKN2A deletion was an independent prognostic marker for poorer OS (p= 0.036) and PFS (p= 0.005), MGMTp methylation had a trend of superseding CDKN2A deletion (p= 0.055) for prognostication and G-CIMP subgroups could similarly partially supersede CDKN2A deletion (p= 0.582). Hence, CDKN2A deletion should be supplemented with these two biomarkers for finer prognostication. Targeted sequencing (n= 55) showed that there were more ATRX (35/55, 64%), TP53 (31/55, 56%), KMT2D (18/55, 33%), POLE (11/55, 20%) and MSH6 (7/55, 13%) mutations, but fewer TERTp (3/69, 4%) and PTEN (1/55, 2%) mutations than IDH-wildtype glioblastomas as from literature and databases. CNVs revealed by methylomes (n= 53) and mutations (n= 55) showed that there were more PDGFRA (amplification: 9/53, 17%, mutation: 10/55, 18%) alterations, but fewer MET (amplification: 3/53, 6%, mutation: 4/55, 7%) alterations and hypermutated (6/55, 11%) cases than IDH-mutant secondary glioblastomas from literature. GISTIC analysis revealed amplifications of CCND2, CDK4, MYC, and PDGFRA, deletions of CDKN2A, RB1, and chromosome 10q to be significant CNVs (q< 0.05). There were few EGFR amplifications (2/53, 4%), which was different from regular glioblastomas. RNA sequencing (n= 42) showed few fusions (4/42, 10%), which was different from IDH-mutant secondary glioblastomas.

Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3503-3503 ◽  
Author(s):  
Alan P. Venook ◽  
Fang-Shu Ou ◽  
Heinz-Josef Lenz ◽  
Omar Kabbarah ◽  
Xueping Qu ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Molecular Subtype ◽  
Progression Free Survival ◽  
Molecular Data ◽  
Tumor Location ◽  
Tumor Burden ◽  
Independent Prognostic Marker ◽  
Molecular Features ◽  
Metastatic Sites ◽  
The Impact

3503 Background: 80405 found no OS or Progression Free Survival (PFS) difference when bevacizumab (BV) or cetuximab (Cet) was added to 1st-line FOLFOX or FOLFIRI in All RAS wild type (wt) mCRC pts. There was a significant 1° side by biologic interaction (P int: OS = 0.008, PFS = 0.001) favoring pts with left-sided (L) 1°. Analyses of 1° tumors beyond All RAS includes Consensus Molecular Subtype (CMS), BRAF and MSI. (CMS results - see Lenz et al; BRAF -see Innocenti et al) We asked whether 1° tumor location - L vs right (R) - is an independent prognostic marker when these other molecular features are considered. Methods: We used a Cox proportional hazard model stratified by prior XRT and +/- adjuvant chemo; adjusted for age, gender, synchronous vs metachronous, CMS, MSI and BRAF status. Pts with transverse (T) tumors were excluded in this analysis. Results: Sidedness was determined in 782 pts (L - 472; R - 256; T -54). Molecular data from 728 pts (with L - and R-sided 1°s) was available as follows: KRAS -- 291, NRAS -393, BRAF - 393, MSI - 378, CMS - 533. L vs R mOS: 32.9 v 19.6 months (mo) (p < 0.0001). See Table for OS results in All RAS / BRAF wt and BRAF mutant (mut) pts. Sidedness (R vs L) is an independent prognostic marker even after adjusting for all these molecular features: HR = 1.392 (1.032, 1.878), p = 0.031. Conclusions: Primary tumor location is an independent prognostic factor when adjusted for age, gender, synchronous/metachronous, CMS, MSI and BRAF status. We are exploring clinical variables such as tumor burden, metastatic sites and measurability of disease in an attempt to explain the impact of sidedness. Support: U10CA188021, U10CA180882. Eli Lilly and Co, Genentech/Roche, Pfizer, Sanofi. Clinical trial information: NCT002655850. [Table: see text]

The AST/ALT Ratio Is an Independent Prognostic Marker for Disease-free Survival in Stage II and III Colorectal Carcinoma

2021 ◽  
Vol 41 (1) ◽  
pp. 429-436
Author(s):  
LUKAS SCHEIPNER ◽  
MARIA ANNA SMOLLE ◽  
DOMINIK BARTH ◽  
FLORIAN POSCH ◽  
MICHAEL STOTZ ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Prognostic Marker ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Independent Prognostic Marker ◽  
Disease Free

scholarly journals 662. Identification of Clinically Relevant Microbes with the MasSpec Pen

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S386-S387
Author(s):  
Sydney C Povilaitis ◽  
Ashish D Chakraborty ◽  
Rachel D Downey ◽  
Sarmistha Bhaduri Hauger ◽  
Livia Eberlin
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometer ◽  
Model Performance ◽  
Sample Surface ◽  
Clinical Analysis ◽  
Ambient Ionization ◽  
Rapid Identification ◽  
Negative Ion ◽  
Ionization Mass ◽  
Molecular Features

Abstract Background In the age of antimicrobial resistance, rapid identification of infectious agents is critical for antimicrobial stewardship and effective therapy. To this end, ambient ionization mass spectrometry techniques have been applied for rapid identification of microbes directly from culture isolates. We have developed a handheld, mass spectrometry-based device, the MasSpec Pen, that permits direct molecular analysis of a biological sample in seconds (Scheme 1). Here, we employ the MasSpec Pen to identify clinically relevant microbes directly from culture isolates. Methods Staphylococcus aureus, Staphylococcus epidermidis, Group A and B Streptococcus, Kingella kingae (K.k), and Pseudomonas aeruginosa (P.a) were cultured on 5% sheep’s blood nutrient agar at 37 °C overnight. Colonies were transferred to a glass slide where they were analyzed directly with the MasSpec Pen coupled to a Q Exactive mass spectrometer (Thermo Scientific) in negative ion mode. For MasSpec Pen analysis, a 10 µL droplet of water was held in contact with the sample surface for 3 seconds and then aspirated to the mass spectrometer for analysis. Data was normalized and the molecular features resulting from the analysis solvent and nutrient medium were removed. The least absolute shrinkage and selection operator (lasso) statistical method was used to build classification models for prediction of bacterial identity. Model performance was evaluated by leave-one-out cross-validation and a validation set of samples. Scheme 1: MasSpec Pen workflow Results Various small molecules were detected including metabolites and glycerophospholipid species. The mass spectral profiles for each species exhibited qualitative differences among them (Figure 1). Additionally, several quorum-sensing molecules were observed in P.a. including hydroxy-heptyl-quinoline (m/z 242.155). Lasso statistical classifiers were created to differentiate organisms at the level of Gram type, genus, and species with each model comprised of a sparse set of molecular features. Accuracies of 90% or greater were achieved for all lasso models and as high as 98% for the differentiation of Staphylococcus (Staph.) and Streptococcus (Strep.). Figure 1: Molecular profiles of species analyzed Figure 2: Statistical classification results Conclusion These results demonstrate the potential of the MasSpec Pen as a tool for clinical analysis of infected biospecimens. Disclosures Sydney C. Povilaitis, BA, MS Pen Technologies, Inc. (Other Financial or Material Support, Patent) Livia Eberlin, PhD, MS Pen Technolpogies, Inc. (Board Member, Shareholder)

scholarly journals Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients

2013 ◽  
Vol 18 (4) ◽  
pp. 447-454 ◽  
Author(s):  
Zsigmond M. Jenei ◽  
Gábor Széplaki ◽  
Béla Merkely ◽  
István Karádi ◽  
Endre Zima ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Prognostic Marker ◽  
Independent Prognostic Marker

Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischaemic stroke

2013 ◽  
Vol 126 (5) ◽  
pp. 339-346 ◽  
Author(s):  
Wen-Jun Tu ◽  
Sheng-Jie Zhao ◽  
Dong-Jiang Xu ◽  
Hui Chen
Keyword(s):  
Ischaemic Stroke ◽  
Functional Outcome ◽  
Prognostic Marker ◽  
Acute Ischaemic Stroke ◽  
Chinese Patients ◽  
Short Term ◽  
Hydroxyvitamin D ◽  
Independent Prognostic Marker ◽  
Vitamin D Levels ◽  
25 Hydroxyvitamin D

Low vitamin D levels have been reported to contribute to the risk of cardiovascular events and mortality, especially stroke. In the present study we therefore evaluated the short-term prognostic value of serum 25(OH)D (25-hydroxyvitamin D) in Chinese patients with AIS (acute ischaemic stroke). From February 2010 to September 2012, consecutive stroke patients admitted to the emergency department at two hospitals in Beijing, China were identified. Clinical information was collected, and the serum concentration of 25(OH)D and NIHSS (National Institutes of Health Stroke Scale) were measured at the time of admission. Short-term functional outcome was measured using a modified Rankin Scale (mRS) at 90 days after admission. Multivariate analyses were performed using logistic regression models. During the inclusion period, 231 patients were diagnosed as having AIS, and 220 completed follow-up. The median serum 25(OH)D level was significantly lower in patients with AIS compared with normal controls [14.2 (10.2–18.9) ng/ml compared with 17.9 (12.5–22.9) ng/ml; P<0.001; values are medians (interquartile range)]. 25(OH)D was an independent prognostic marker of short-term functional outcome and death {0.79 (0.73–0.85) and 0.70 (0.50–0.98) respectively [values are odds rations (95% confidence intervals)]; P<0.01 for both, adjusted for NHISS, other predictors and vascular risk factors} in patients with AIS. In ROC (receiver operating characteristic) curve analysis, the prognostic accuracy of 25(OH)D was higher compared with all of the other serum predictors and was in the range of NIHSS score. In conclusion, these findings suggest that 25(OH)D is an independent prognostic marker for death and functional outcome within 90 days in Chinese patients with AIS even after adjusting for possible confounding factors

Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables

Lung Cancer ◽  
2002 ◽  
Vol 37 (3) ◽  
pp. 235-240 ◽  
Author(s):  
Daniel E.B Swinson ◽  
J.Louise Jones ◽  
Donna Richardson ◽  
Giles Cox ◽  
John G Edwards ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Prognostic Marker ◽  
Cell Lung Cancer ◽  
Tumour Necrosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Independent Prognostic Marker ◽  
Biological Variables
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