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Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer

Overview of attention for article published in BMC Medical Genomics, October 2016
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Title
Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer
Published in
BMC Medical Genomics, October 2016
DOI 10.1186/s12920-016-0225-2
Pubmed ID
Authors

Bernard Omolo, Mingli Yang, Fang Yin Lo, Michael J. Schell, Sharon Austin, Kellie Howard, Anup Madan, Timothy J. Yeatman

Abstract

The KRAS gene is mutated in about 40 % of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistance to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60 % of patients with a wild type KRAS fail to respond to EGFRi combination therapies, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter™ (NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq (t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE (r = 0.233, p = 0.090); (2) NanoS_FFPE (r = 0.608, p < 0.0001); (3) RNA-Acc_FFPE (r = 0.175, p = 0.21); (4) t-RNA_FFPE (r = -0.237, p = 0.085); (5) and t-RNA (r = -0.012, p = 0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n = 15) and genes (n = 2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r = 0.672, p < 0.0001); NanoS_FFPE (r = 0.738, p < 0.0001); and RNA-Acc_FFPE (r = 0.483, p = 0.002). Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples.

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Mendeley readers

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Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 28%
Student > Master 6 19%
Other 4 13%
Student > Ph. D. Student 4 13%
Student > Doctoral Student 1 3%
Other 2 6%
Unknown 6 19%
Readers by discipline Count As %
Medicine and Dentistry 6 19%
Agricultural and Biological Sciences 5 16%
Biochemistry, Genetics and Molecular Biology 3 9%
Computer Science 2 6%
Psychology 2 6%
Other 2 6%
Unknown 12 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 October 2016.
All research outputs
#18,478,448
of 22,896,955 outputs
Outputs from BMC Medical Genomics
#863
of 1,225 outputs
Outputs of similar age
#238,856
of 315,882 outputs
Outputs of similar age from BMC Medical Genomics
#6
of 8 outputs
Altmetric has tracked 22,896,955 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,225 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
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