Evidence map›Paper›PMID 38745208›Full record

ArticleBreast cancer research : BCR2024

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection.

Praveen-Kumar Raj-Kumar, Xiaoying Lin, Tao Liu, Lori A Sturtz, Marina A Gritsenko, Vladislav A Petyuk, Tyler J Sagendorf, Brenda Deyarmin, Jianfang Liu, Anupama Praveen-Kumar and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Review
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  5. Review
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

30 authors.

Praveen-Kumar Raj-KumarChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Xiaoying LinChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Tao LiuPacific Northwest National Laboratory, Richland, WA, USA.
Lori A SturtzChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Marina A GritsenkoPacific Northwest National Laboratory, Richland, WA, USA.
Vladislav A PetyukPacific Northwest National Laboratory, Richland, WA, USA.
Tyler J SagendorfPacific Northwest National Laboratory, Richland, WA, USA.
Brenda DeyarminChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Jianfang LiuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Anupama Praveen-KumarChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Guisong WangMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Jason E McDermottPacific Northwest National Laboratory, Richland, WA, USA.
Anil K ShuklaPacific Northwest National Laboratory, Richland, WA, USA.
Ronald J MoorePacific Northwest National Laboratory, Richland, WA, USA.
Matthew E MonroePacific Northwest National Laboratory, Richland, WA, USA.
Bobbie-Jo M Webb-RobertsonPacific Northwest National Laboratory, Richland, WA, USA.
Jeffrey A HookeMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Leigh Fantacone-CampbellMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Brad MostollerChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Leonid KvecherChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Jennifer KaneChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Jennifer MelleyChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Stella SomiariChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Patrick Soon-ShiongNantWorks, Culver City, CA, USA.
Richard D SmithPacific Northwest National Laboratory, Richland, WA, USA.
Richard J MuralChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Karin D RodlandPacific Northwest National Laboratory, Richland, WA, USA.
Craig D ShriverMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. craig.shriver@usuhs.edu.
Albert J KovatichMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Hai HuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA. h.hu@wriwindber.org.

Funding

Henry M. Jackson Foundation W81XWH-12-2-0050Uniformed Services University of the Health Sciences HU0001-16-2-0004
6 · The paper itself

Abstract

backgroundBreast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors.

methodsWe retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers.

resultsWe observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors.

conclusionsThis study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Indexed as

Biomarkers, TumorBreast NeoplasmsProteogenomicsAdultAgedFemaleHumansLaser Capture MicrodissectionMiddle AgedMutationPrognosisProteomicsRetrospective StudiesBiomarkers, TumorBreast cancerLaser microdissectionPhosphoproteomicsProteogenomics

Identifiers

PMID38745208
PMCPMC11094977

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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.