Obesity-associated changes in molecular biology of primary breast cancer

被引：15

作者：

Nguyen, Ha-Linh ^{[1
]}

Geukens, Tatjana ^{[1
]}

Maetens, Marion ^{[1
]}

Aparicio, Samuel ^{[2
,3
]}

Bassez, Ayse ^{[4
,5
]}

Borg, Ake ^{[6
,7
,8
,9
]}

Brock, Jane ^{[10
]}

Broeks, Annegien ^{[11
,12
]}

Caldas, Carlos ^{[13
,14
,18
]}

Cardoso, Fatima ^{[15
]}

De Schepper, Maxim ^{[1
]}

Delorenzi, Mauro ^{[16
,17
]}

Drukker, Caroline A.

Glas, Annuska M. ^{[19
]}

Green, Andrew R. ^{[20
]}

Isnaldi, Edoardo ^{[1
]}

Eyfjoro, Jorunn ^{[21
]}

Khout, Hazem ^{[22
]}

Knappskog, Stian ^{[23
,24
]}

Krishnamurthy, Savitri ^{[25
]}

Lakhani, Sunil R. ^{[26
,27
]}

Langerod, Anita ^{[28
]}

Martens, John W. M. ^{[29
]}

Reed, Amy E. McCart ^{[26
]}

Murphy, Leigh ^{[30
,31
]}

Naulaerts, Stefan ^{[32
]}

Nik-Zainal, Serena ^{[33
,34
]}

Nevelsteen, Ines ^{[35
]}

Neven, Patrick ^{[36
]}

Piccart, Martine ^{[37
,38
]}

Poncet, Coralie ^{[39
,42
]}

Punie, Kevin ^{[40
,41
]}

Purdie, Colin

Rakha, Emad A. ^{[43
,44
]}

Richardson, Andrea

Rutgers, Emiel ^{[46
]}

Vincent-Salomon, Anne ^{[45
,47
]}

Simpson, Peter T. ^{[26
]}

Schmidt, Marjanka K. ^{[48
]}

Sotiriou, Christos ^{[49
]}

Span, Paul N. ^{[50
]}

Tan, Kiat Tee Benita ^{[51
,52
,53
]}

Thompson, Alastair ^{[54
]}

Tommasi, Stefania ^{[55
]}

Van Baelen, Karen ^{[1
]}

Van de Vijver, Marc ^{[56
]}

Van Laere, Steven ^{[57
]}

van't Veer, Laura ^{[58
]}

Viale, Giuseppe ^{[59
,60
]}

Viari, Alain ^{[61
]}

机构：

[1] Katholieke Univ Leuven, Lab Translat Breast Canc Res, Dept Oncol, Leuven, Belgium

[2] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada

[3] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[4] Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium

[5] VIB Ctr Canc Biol, Leuven, Belgium

[6] Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden

[7] Lund Univ, Canc Ctr Lund, Lund, Sweden

[8] Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden

[9] Lund Univ, Dept Clin Sci, SCIBLU Genom, Lund, Sweden

[10] Brigham & Womens Hosp, Dept Pathol, Boston, MA USA

[11] Netherlands Canc Inst, Dept Core Facil Mol Pathol & Biobanking, Antoni van Leeuwenhoek, Amsterdam, Netherlands

[12] Netherlands Canc Inst, Dept Mol Pathol & Biobanking, Antoni van Leeuwenhoek, Amsterdam, Netherlands

[13] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[14] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge, England

[15] Champalimaud Fdn, Champalimaud Clin Ctr, Breast Unit, Lisbon, Portugal

[16] Univ Lausanne, Dept Oncol, Epalinges, Switzerland

[17] SIB Swiss Inst Bioinformat, Bioinformat Core Facil, Lausanne, Switzerland

[18] Antoni van Leeuwenhoek Hosp, Dept Surg Oncol, Amsterdam, Netherlands

[19] Agendia, Amsterdam, Netherlands

[20] Univ Nottingham, Sch Med, Nottingham Breast Canc Res Ctr, Nottingham, England

[21] Univ Iceland, Sch Hlth Sci, Biomed Ctr, Fac Med, Reykjavik, Iceland

[22] Univ Hosp Leicester NHS Trust, Glenfield Hosp, Dept Breast Surg, Leicester, Leics, England

[23] Univ Bergen, Dept Clin Sci, Fac Med, Bergen, Norway

[24] Haukeland Hosp, Dept Oncol, Bergen, Norway

[25] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[26] Univ Queensland, UQ Ctr Clin Res, Fac Med, Herston, Qld, Australia

[27] Royal Brisbane & Womens Hosp, Pathol Queensland, Herston, Qld, Australia

[28] Oslo Univ Hosp, Inst Canc Res, Depr Canc Genet, Ullernchausseen Oslo, Oslo, Norway

[29] Erasmus MC, Dept Med Oncol & Canc Genom Netherlands, Erasmus MC Canc Inst, Rotterdam, Netherlands

[30] Univ Manitoba, Winnipeg, MB, Canada

[31] Canc Care Manitoba Res Inst, Winnipeg, MB, Canada

[32] Katholieke Univ Leuven, Lab Cell Stress & Immun, Dept Cellular Mol Med, Leuven, Belgium

[33] Univ Cambridge, Sch Clin Med, Dept Med Genet, Cambridge, England

[34] Univ Cambridge, Sch Clin Med, MRC Canc Unit, Cambridge, England

[35] Katholieke Univ Leuven, Dept Surg Oncol, Univ Hosp Leuven, Leuven, Belgium

[36] Univ Hosp Leuven, Dept Gynecol Oncol, Leuven, Belgium

[37] Inst Jules Bordet, Brussels, Belgium

[38] Univ Libre Bruxelles, Brussels, Belgium

[39] European Org Res & Treatment Canc EORTC Headquate, Brussels, Belgium

[40] Leuven Canc Inst, Dept Gen Med Oncol & Multidisciplinary, Breast Unit, Leuven, Belgium

[41] Univ Hosp Leuven, Leuven, Belgium

[42] Univ Dundee, Dept Pathol, NHS Tayside, Dundee, Scotland

[43] Univ Nottingham, Sch Med, Div Canc & Stem Cells, Nottingham, England

[44] Nottingham Univ Hosp NHS Trust, City Hosp Campus, Dept Histopathol, Nottingham, England

[45] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[46] Netherlands Canc Inst, Dept Surg Oncol, Amsterdam, Netherlands

[47] PSL Res Univ, Diagnost & Theranost Med Div, Inst Curie, Paris, France

[48] Netherlands Canc Inst, Divis Mol Pathol, Antoni van Leeuwenhoek Hosp, Amsterdam, Netherlands

[49] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium

[50] Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, Nijmegen, Netherlands

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

欧洲研究理事会; 英国惠康基金;

关键词：

SOMATIC MUTATIONS; BODY-SIZE; EXPRESSION; RISK; GENE; SIGNATURES; HALLMARKS; PATHWAYS; ESTROGEN; TARGET;

D O I：

10.1038/s41467-023-39996-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.

引用

页数：17

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