Cited by 162Breast Cancer Treatment StudiesAdvanced Proteomics Techniques and ApplicationsBioinformatics and Genomic Networks

Integrated proteotranscriptomics of breast cancer reveals globally increased protein-mRNA concordance associated with subtypes and survival

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Tang, Wei, Zhou, Ming, Dorsey, Tiffany H., Prieto, DaRue A., Wang, Xin W., Ruppin, Eytan, Veenstra, Timothy D., Ambs, Stefan·2018·Genome Medicine

Abstract

Background: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis. Methods: We applied a quantitative liquid chromatography/mass spectrometry-based proteome analysis using an untargeted approach and analyzed protein extracts from 65 breast tumors and 53 adjacent non-cancerous tissues. Additional gene expression data from Affymetrix Gene Chip Human Gene ST Arrays were available for 59 tumors and 38 non-cancerous tissues in our study. We then applied an integrated analysis of the proteomic and transcriptomic data to examine relationships between them, disease characteristics, and patient survival. Findings were validated in a second dataset using proteome and transcriptome data from “The Cancer Genome Atlas” and the Clinical Proteomic Tumor Analysis Consortium. Results: We found that the proteome describes differences between cancerous and non-cancerous tissues that are not revealed by the transcriptome. The proteome, but not the transcriptome, revealed an activation of infection-related signal pathways in basal-like and triple-negative tumors. We also observed that proteins rather than mRNAs are increased in tumors and show that this observation could be related to shortening of the 3′ untranslated region of mRNAs in tumors. The integrated analysis of the two technologies further revealed a global increase in protein-mRNA concordance in tumors. Highly correlated protein-gene pairs were enriched in protein processing and disease metabolic pathways. The increased concordance between transcript and protein levels was additionally associated with aggressive disease, including basal-like/triple-negative tumors, and decreased patient survival. We also uncovered a strong positive association between protein-mRNA concordance and proliferation of tumors. Finally, we observed that protein expression profiles co-segregate with a Myc activation signature and separate breast tumors into two subgroups with different survival outcomes. Conclusions: Our study provides new insights into the relationship between protein and mRNA expression in breast cancer and shows that an integrated analysis of the proteome and transcriptome has the potential of uncovering novel disease characteristics.

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Crossref · 10.1186/s13073-018-0602-x

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  • In a dataset of 61 unselected breast cancer patients, aggregate survival analysis showed no significant difference in overall survival between patients with high vs. low tumor SLFN11 expression (HR = 1.24, p = 0.608).

    “In a dataset of 61 unselected breast cancer patients [10], aggregate survival analysis showed no significant difference in overall survival (OS) between patients with high vs. low tumor SLFN11 expression (HR = 1.24, p = 0.608) (Fig 3A).”

    From Integrated pan-cancer gene expression and drug sensitivity analysis reveals SLFN11 mRNA as a solid tumor biomarker predictive of sensitivity to DNA-damaging chemotherapy (2019) · cites this paper as [10]

    The Results section on proteomic profiling describes a breast-cancer dataset, but reports 65 tumors, not 61 patients. The citation is attached to the dataset description; the SLFN11 survival analysis is presented as the citing authors’ own result in Fig. 3A, so it need not appear in this source. Our copy does not establish the stated 61-patient subset or that patients were unselected. (LLM, conf=0.83)

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1 of the 37 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [32]de Sousa AR Penalva LO Marcotte EM Vogel C Global signatures of protein and mRNA expression levels Mol BioSyst 2009 5 1512 1526 20023718 PMC4089977

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Authors
Tang, W., Zhou, M., Dorsey, T. H., Prieto, D. A., Wang, X. W., Ruppin, E., Veenstra, T. D., & Ambs, S.
Affiliations
  • National Institutes of Health (US)
  • Frederick National Laboratory for Cancer Research (US)
  • National Cancer Institute (US)
Corresponding author
Ambs, Stefan
Venue
Genome Medicine
Published
2018-12-03
Volume
10
Issue
1
Pages
94-94
ISSN
1756-994X (ISSN-L)
OpenAlex
W2902072367
Cited by
162
References
37
Citations by year
2026: 7 · 2025: 16 · 2024: 20 · 2023: 44 · 2022: 25 · 2021: 35 · 2020: 9 · 2019: 6
FWCI
3.78
Type
journal article
Language
en
Open access
Locations
  • Genome Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Cancer Institute (ZIA BC 010887)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
breast cancer, proteotranscriptomics, breast cancer subtypes, basal-like breast cancer, triple-negative breast cancer, tumor cell proliferation, patient survival
MeSH terms
Breast Neoplasms, Chromatography, Liquid, Female, Humans, Mass Spectrometry, Signal Transduction, Gene Expression Regulation, Neoplastic, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Proteomics

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