Correlations of mRNA expression levels of genes in the targeted pathways and Kras mutation status in patients with colorectal cancer.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 10641-10641 ◽  
Author(s):  
D. Yang ◽  
W. Zhang ◽  
T. Winder ◽  
P. O. Bohanes ◽  
Y. Ning ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Kras Mutation ◽  
Mutation Status ◽  
Expression Levels ◽  
Kras Mutation Status ◽  
Mrna Expression Levels

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

scholarly journals Cigarette Smoking and Colorectal Cancer Risk by KRAS Mutation Status Among Older Women

2012 ◽  
Vol 107 (5) ◽  
pp. 782-789 ◽  
Author(s):  
N J Samadder ◽  
Robert A Vierkant ◽  
Lori S Tillmans ◽  
Alice H Wang ◽  
Charles F Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Cigarette Smoking ◽  
Older Women ◽  
Kras Mutation ◽  
Colorectal Cancer Risk ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals KRAS mutation status, comorbidity, and mortality in patients with metastatic colorectal cancer in Denmark

2018 ◽  
Vol 57 (12) ◽  
pp. 1727-1729
Author(s):  
Anne Gulbech Ording ◽  
Buket Öztürk ◽  
Karen-Lise Garm Spindler ◽  
Henrik Toft Sørensen ◽  
Margaret McCusker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Mutation Status ◽  
Kras Mutation Status

High clusterin (CLU) mRNA expression levels in tumors of colorectal cancer patients predict a poor prognostic outcome

2020 ◽  
Vol 75 ◽  
pp. 62-69 ◽  
Author(s):  
Pinelopi I. Artemaki ◽  
Aimilia D. Sklirou ◽  
Christos K. Kontos ◽  
Aikaterini-Anna Liosi ◽  
Despoina D. Gianniou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Expression Levels ◽  
Prognostic Outcome ◽  
Colorectal Cancer Patients ◽  
Mrna Expression Levels

scholarly journals SUVmax and metabolic tumor volume: surrogate image biomarkers of KRAS mutation status in colorectal cancer

2019 ◽  
Vol Volume 12 ◽  
pp. 2115-2121 ◽  
Author(s):  
Ying Lv ◽  
Xin Wang ◽  
Lerong Liang ◽  
Lei Wang ◽  
Jie Lu
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals Relationships between KRAS mutation status and baseline radiographic distribution of disease in patients with stage IV colorectal cancer

2014 ◽  
Vol 39 (6) ◽  
pp. 1261-1266 ◽  
Author(s):  
Michael H. Rosenthal ◽  
Kyung Won Kim ◽  
Charles S. Fuchs ◽  
Jeffrey A. Meyerhardt ◽  
Nikhil H. Ramaiya
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Stage Iv ◽  
Mutation Status ◽  
Stage Iv Colorectal Cancer ◽  
Kras Mutation Status

DEPENDENCE OF YKL-40 mRNA TISSUE LEVELS ON KRAS MUTATION STATUS IN COLORECTAL CANCER - PRELIMINARY RESULTS

2015 ◽  
Vol 1 (2) ◽  
pp. 43 ◽  
Author(s):  
Yana Feodorova ◽  
Dessislava Tashkova ◽  
Kiril Simitchiev ◽  
Anton Todorov ◽  
Gancho Kostov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Mutation Status ◽  
Preliminary Results ◽  
Tissue Levels ◽  
Kras Mutation Status

Expression of Ara-C Metabolizing Enzymes Mediates in Vitro Sensitivity to Ara-C in Primary AML Cells From Patients with Denovo AML,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3481-3481
Author(s):  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Ashok kumar Jayavelu ◽  
Shaji R Velayudhan ◽  
Rayaz Ahmed ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Candidate Genes ◽  
P Value ◽  
Mrna Levels ◽  
Wild Type ◽  
Mutation Status ◽  
Expression Levels ◽  
In Vitro Sensitivity ◽  
Mrna Expression Levels

Abstract Abstract 3481 Wide inter-individual variation in terms of treatment outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (ara-C) and daunorubicin. The pre-requisite for the cytotoxic action of pro-drug Ara-C is the enzymatic conversion to its active tri-phosphorylated form ara-CTP. Many drug activating (Deoxycytidine kinase (dCK) and human Equilibrative Nucleoside Transporter 1 (hENT1) and deactivating (Cytidine deaminase (CDA), 5'nucleotidase (NT5C2) genes and ribonucleoside reductase (RRM1), which are involved in transport and biotransformation of cytarabine contribute to the variation in ara-C sensitivity in AML patients. FLT3-ITD and NPM1 mutations act as major poor and good prognostic markers respectively in cytogenetically normal AML. The effect of these mutations in ara-C metabolism remains to be elucidated. The present study aims to determine independent as well as the combined effect of ara-C metabolizing genes mRNA expression on in-vitro ara-C cytotoxicity and the role of FLT3-ITD and NPM mutations on mRNA expression of these genes. Diagnostic bone marrow sample (median blasts 65%; range 21 – 98%) from 98 adult patients with de novo AML (other than AML-M3) were included in this study. mRNA expression levels for each target gene relative to housekeeping gene GAPDH was analyzed using Taqman based gene expression assays. In vitro cytotoxicity was assessed using MTT cell viability assay and IC-50 was calculated. In vitro sensitivity or resistance was classified on the basis of the IC-50 values <6uM and >6uM ara-C respectively. FLT3 ITD and NPM mutation status at diagnosis were determined through PCR followed by Genescan analysis using genomic DNA samples. Type of NPM mutation was identified by sequencing. When ara-C IC-50 values were compared with the mRNA expression levels of these candidate genes, Ara-C sensitive samples (n= 30; IC-50 < 6uM) showed significantly higher mRNA expression of dCK and hENT1 compared to those with Ara-C resistance (n=51) IC50 >6uM (median 314 (61.56 – 1232) vs. 180 (31.87 – 749.2); p = 0.0004 and median 172.1 (44.12 – 657.6) vs. 96.19 (37.49 – 432.4), p= 0.0008 respectively. RRM1 and NT5C2 did not show any association with in vitro Ara-C cytotoxicity, while CDA showed a trend towards association with lower CDA expression in ara-C sensitive samples. Based on these findings we put forward Ara-C resistance index (RI). RI is calculated by the formula RI = ΔCT (dCK X ENT1)/ ΔCT CDA. (Smaller ΔCT value= higher mRNA expression). RI values were significantly higher in resistant (IC50 >6uM) compared to sensitive cells (median: 6.084; range 1.89–11.82) vs. 3.702 (1.89–9.80); p=<0.0001). This association should now be validated in an independent cohort. Effects of NPM and FLT3 mutation status on Ara-C metabolizing genes were then evaluated. No significant association was found between FLT3-ITD status and the mRNA expression of these candidate genes. Interestingly, dCK mRNA levels were significantly higher in samples with NPM mutation (n=39) compared to NPM wild type (n=59); median 272.3 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.01. When analysed separately, patients with NPM type A mutation (n=27) showed significantly higher dCK expression (median 347.4 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.003 compared to those with wild type NPM1. This first report showing an association between expression profiles of ara-C metabolizing genes and NPM mutation should form the basis for evaluating their clinical correlations. Disclosures: No relevant conflicts of interest to declare.

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