Evidence map›Paper›PMID 31856832›Full record

ArticleBMC medical genomics2019

RNA-seq from archival FFPE breast cancer samples: molecular pathway fidelity and novel discovery.

Nathan D Pennock, Sonali Jindal, Wesley Horton, Duanchen Sun, Jayasri Narasimhan, Lucia Carbone, Suzanne S Fei, Robert Searles, Christina A Harrington, Julja Burchard and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Nathan D PennockDepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave, Portland, OR, 97201, USA.
Sonali JindalDepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave, Portland, OR, 97201, USA.
Wesley HortonDepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave, Portland, OR, 97201, USA.
Duanchen SunComputational Biology Program, Oregon Health & Science University, Portland, OR, 97201, USA.
Jayasri NarasimhanDepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave, Portland, OR, 97201, USA.
Lucia CarboneDivision of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
Suzanne S FeiBioinformatics & Biostatistics Core, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
Robert SearlesIntegrated Genomics Laboratory, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, Portland, OR, 97239, USA.
Christina A HarringtonIntegrated Genomics Laboratory, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, Portland, OR, 97239, USA.
Julja BurchardComputational Biology Program, Oregon Health & Science University, Portland, OR, 97201, USA.
Sheila WeinmannCenter for Health Research, Kaiser Permanente Northwest, Portland, OR, 97278, USA.
Pepper SchedinDepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave, Portland, OR, 97201, USA. schedin@ohsu.edu.ORCID 0000-0003-4244-987X
Zheng XiaComputational Biology Program, Oregon Health & Science University, Portland, OR, 97201, USA. xiaz@ohsu.edu.
Oregon Health & Science University · USOregon National Primate Research Center · USKaiser Permanente Center for Health Research · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5M
NSAIDs During Postpartum Involution for Breast Cancer ChemopreventionR01CA169175 · NCI · UNIVERSITY OF COLORADO DENVER · PI SCHEDIN, PEPPER J · 2013 to 2024
$4.8M
In Silico Screening of Alternative Polyadenylation Regulators in CancersK01LM012877 · NLM · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIA, ZHENG · 2018 to 2020
$428k
HaemAPA: Characterizing alternative polyadenylation in human blood cellsR21HL145426 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIA, ZHENG · 2019 to 2020
$231k
NCI NIH HHS P30 CA046934NCI NIH HHS P30 CA069533NCI NIH HHS R01 CA169175NHLBI NIH HHS R21 HL145426NIH HHS P51 OD011092NLM NIH HHS K01 LM012877
6 · The paper itself

Abstract

backgroundFormalin-fixed, paraffin-embedded (FFPE) tissues for RNA-seq have advantages over fresh frozen tissue including abundance and availability, connection to rich clinical data, and association with patient outcomes. However, FFPE-derived RNA is highly degraded and chemically modified, which impacts its utility as a faithful source for biological inquiry.

methodsTrue archival FFPE breast cancer cases (n = 58), stored at room temperature for 2-23 years, were utilized to identify key steps in tissue selection, RNA isolation, and library choice. Gene expression fidelity was evaluated by comparing FFPE data to public data obtained from fresh tissues, and by employing single-gene, gene set and transcription network-based regulon analyses.

resultsWe report a single 10 μm section of breast tissue yields sufficient RNA for RNA-seq, and a relationship between RNA quality and block age that was not linear. We find single-gene analysis is limiting with FFPE tissues, while targeted gene set approaches effectively distinguish ER+ from ER- breast cancers. Novel utilization of regulon analysis identified the transcription factor KDM4B to associate with ER+ disease, with KDM4B regulon activity and gene expression having prognostic significance in an independent cohort of ER+ cases.

conclusionOur results, which outline a robust FFPE-RNA-seq pipeline for broad use, support utilizing FFPE tissues to address key questions in the breast cancer field, including the delineation between indolent and life-threatening disease, biological stratification and molecular mechanisms of treatment resistance.

Indexed as

FormaldehydeParaffin EmbeddingRNA-SeqTissue FixationBreast NeoplasmsHumansReceptors, EstrogenSignal TransductionFormaldehydeReceptors, EstrogenArchival tissueBreast CancerEstrogen receptorFFPEFormalin fixed paraffin embeddedKDM4BRegulonRNA-seqRNA-Seq, genomicsRNA sequencing

Identifiers

PMID31856832
PMCPMC6924022
OpenAlexW2994875017

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.