Proteomic analysis of breast tumors confirms the mRNA intrinsic molecular subtypes using different classifiers : A large-scale analysis of fresh frozen tissue samples

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Waldemarson, SofiaLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH (författare)

Proteomic analysis of breast tumors confirms the mRNA intrinsic molecular subtypes using different classifiers : A large-scale analysis of fresh frozen tissue samples

Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

2016-06-29
Springer Science and Business Media LLC,2016

Nummerbeteckningar

LIBRIS-ID:oai:lup.lub.lu.se:a8cefef2-1c9c-4a37-bf1e-0e1fcd869bc5
https://lup.lub.lu.se/record/a8cefef2-1c9c-4a37-bf1e-0e1fcd869bc5URI
https://doi.org/10.1186/s13058-016-0732-2DOI

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Språk:engelska
Sammanfattning på:engelska

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Anmärkningar

Background: Breast cancer is a complex and heterogeneous disease that is usually characterized by histological parameters such as tumor size, cellular arrangements/rearrangments, necrosis, nuclear grade and the mitotic index, leading to a set of around twenty subtypes. Together with clinical markers such as hormone receptor status, this classification has considerable prognostic value but there is a large variation in patient response to therapy. Gene expression profiling has provided molecular profiles characteristic of distinct subtypes of breast cancer that reflect the divergent cellular origins and degree of progression. Methods: Here we present a large-scale proteomic and transcriptomic profiling study of 477 sporadic and hereditary breast cancer tumors with matching mRNA expression analysis. Unsupervised hierarchal clustering was performed and selected proteins from large-scale tandem mass spectrometry (MS/MS) analysis were transferred into a highly multiplexed targeted selected reaction monitoring assay to classify tumors using a hierarchal cluster and support vector machine with leave one out cross-validation. Results: The subgroups formed upon unsupervised clustering agree very well with groups found at transcriptional level; however, the classifiers (genes or their respective protein products) differ almost entirely between the two datasets. In-depth analysis shows clear differences in pathways unique to each type, which may lie behind their different clinical outcomes. Targeted mass spectrometry analysis and supervised clustering correlate very well with subgroups determined by RNA classification and show convincing agreement with clinical parameters. Conclusions: This work demonstrates the merits of protein expression profiling for breast cancer stratification. These findings have important implications for the use of genomics and expression analysis for the prediction of protein expression, such as receptor status and drug target expression. The highly multiplexed MS assay is easily implemented in standard clinical chemistry practice, allowing rapid and cheap characterization of tumor tissue suitable for directing the choice of treatment.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Breast cancer
Mass spectrometry
Molecular subtyping
Proteomics
Transcriptomics

Biuppslag (personer, institutioner, konferenser, titlar ...)

Kurbasic, EmilaLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)immu-elk (författare)
Krogh, MortenAmber Biosciences AB(Swepub:lu)thep-mkr (författare)
Cifani, PaoloLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)immu-pci (författare)
Berggård, TordNovo Nordisk A/S(Swepub:lu)bpc-tbe (författare)
Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-abo (författare)
James, PeterLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,University of Turku(Swepub:lu)elma-pja (författare)
Institutionen för immunteknologiInstitutioner vid LTH (creator_code:org_t)

Sammanhörande titlar

Ingår i:Breast Cancer Research: Springer Science and Business Media LLC18:11465-54111465-542X

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Breast Cancer Research (Sök värdpublikationen i LIBRIS)

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Av författaren/redakt...: Waldemarson, Sof ...; Kurbasic, Emila; Krogh, Morten; Cifani, Paolo; Berggård, Tord; Borg, Åke; visa fler...; James, Peter; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: Breast Cancer Re ...

Av lärosätet: Lunds universitet

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