Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Shrabanti Chowdhury; Jacob J. Kennedy; Richard G. Ivey; Oscar D. Murillo; Noshad Hosseini; Xiaoyu Song; Francesca Petralia; Anna Calinawan; Sara R. Savage; Anna B. Berry; Boris Reva; Umut Ozbek; Azra Krek; Weiping Ma; Felipe da Veiga Leprevost; Jiayi Ji; Seungyeul Yoo; Chenwei Lin; Uliana J. Voytovich; Yajue Huang; Sun Hee Lee; Lindsay Bergan; Travis D. Lorentzen; Mehdi Mesri; Henry Rodriguez; Andrew N. Hoofnagle; Zachary T. Herbert; Alexey I. Nesvizhskii; Bing Zhang; Jeffrey R. Whiteaker; David Fenyo; Wilson McKerrow; Joshua Wang; Stephan C. Schürer; Vasileios Stathias; X. Steven Chen; Mary Helen Barcellos-Hoff; Timothy K. Starr; Boris J. Winterhoff; Andrew C. Nelson; Samuel C. Mok; Scott H. Kaufmann; Charles Drescher; Marcin Cieslik; Pei Wang; Michael J. Birrer; Amanda G. Paulovich

doi:10.1016/j.cell.2023.07.004

Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Shrabanti Chowdhury, Jacob J. Kennedy, Richard G. Ivey, Oscar D. Murillo, Noshad Hosseini, Xiaoyu Song, Francesca Petralia, Anna Calinawan, Sara R. Savage, Anna B. Berry, Boris Reva, Umut Ozbek, Azra Krek, Weiping Ma, Felipe da Veiga Leprevost, Jiayi Ji, Seungyeul Yoo, Chenwei Lin, Uliana J. Voytovich, Yajue HuangSun Hee Lee, Lindsay Bergan, Travis D. Lorentzen, Mehdi Mesri, Henry Rodriguez, Andrew N. Hoofnagle, Zachary T. Herbert, Alexey I. Nesvizhskii, Bing Zhang, Jeffrey R. Whiteaker, David Fenyo, Wilson McKerrow, Joshua Wang, Stephan C. Schürer, Vasileios Stathias, X. Steven Chen, Mary Helen Barcellos-Hoff, Timothy K. Starr, Boris J. Winterhoff, Andrew C. Nelson, Samuel C. Mok, Scott H. Kaufmann, Charles Drescher, Marcin Cieslik, Pei Wang, Michael J. Birrer, Amanda G. Paulovich

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24 Scopus citations

Abstract

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.

Original language	English
Pages (from-to)	3476-3498.e35
Journal	Cell
Volume	186
Issue number	16
DOIs	https://doi.org/10.1016/j.cell.2023.07.004
State	Published - 3 Aug 2023

Keywords

chemorefractory
high-grade serous ovarian cancer
machine learning
mass spectrometry
multiple reaction monitoring
platinum
precision oncology
predictive biomarker
prognostic biomarker
proteogenomic

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10.1016/j.cell.2023.07.004

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Chowdhury, S., Kennedy, J. J., Ivey, R. G., Murillo, O. D., Hosseini, N., Song, X., Petralia, F., Calinawan, A., Savage, S. R., Berry, A. B., Reva, B., Ozbek, U., Krek, A., Ma, W., da Veiga Leprevost, F., Ji, J., Yoo, S., Lin, C., Voytovich, U. J., ... Paulovich, A. G. (2023). Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer. Cell, 186(16), 3476-3498.e35. https://doi.org/10.1016/j.cell.2023.07.004

@article{7feb5ade3c1545e0be3cc8098a48355b,

title = "Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer",

abstract = "To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.",

keywords = "chemorefractory, high-grade serous ovarian cancer, machine learning, mass spectrometry, multiple reaction monitoring, platinum, precision oncology, predictive biomarker, prognostic biomarker, proteogenomic",

author = "Shrabanti Chowdhury and Kennedy, {Jacob J.} and Ivey, {Richard G.} and Murillo, {Oscar D.} and Noshad Hosseini and Xiaoyu Song and Francesca Petralia and Anna Calinawan and Savage, {Sara R.} and Berry, {Anna B.} and Boris Reva and Umut Ozbek and Azra Krek and Weiping Ma and {da Veiga Leprevost}, Felipe and Jiayi Ji and Seungyeul Yoo and Chenwei Lin and Voytovich, {Uliana J.} and Yajue Huang and Lee, {Sun Hee} and Lindsay Bergan and Lorentzen, {Travis D.} and Mehdi Mesri and Henry Rodriguez and Hoofnagle, {Andrew N.} and Herbert, {Zachary T.} and Nesvizhskii, {Alexey I.} and Bing Zhang and Whiteaker, {Jeffrey R.} and David Fenyo and Wilson McKerrow and Joshua Wang and Sch{\"u}rer, {Stephan C.} and Vasileios Stathias and Chen, {X. Steven} and Barcellos-Hoff, {Mary Helen} and Starr, {Timothy K.} and Winterhoff, {Boris J.} and Nelson, {Andrew C.} and Mok, {Samuel C.} and Kaufmann, {Scott H.} and Charles Drescher and Marcin Cieslik and Pei Wang and Birrer, {Michael J.} and Paulovich, {Amanda G.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "3",

doi = "10.1016/j.cell.2023.07.004",

language = "English",

volume = "186",

pages = "3476--3498.e35",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "16",

}

Chowdhury, S, Kennedy, JJ, Ivey, RG, Murillo, OD, Hosseini, N, Song, X, Petralia, F, Calinawan, A, Savage, SR, Berry, AB, Reva, B , Ozbek, U, Krek, A, Ma, W, da Veiga Leprevost, F, Ji, J, Yoo, S, Lin, C, Voytovich, UJ, Huang, Y, Lee, SH, Bergan, L, Lorentzen, TD, Mesri, M, Rodriguez, H, Hoofnagle, AN, Herbert, ZT, Nesvizhskii, AI, Zhang, B, Whiteaker, JR, Fenyo, D, McKerrow, W, Wang, J, Schürer, SC, Stathias, V, Chen, XS, Barcellos-Hoff, MH, Starr, TK, Winterhoff, BJ, Nelson, AC, Mok, SC, Kaufmann, SH, Drescher, C, Cieslik, M, Wang, P, Birrer, MJ & Paulovich, AG 2023, 'Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer', Cell, vol. 186, no. 16, pp. 3476-3498.e35. https://doi.org/10.1016/j.cell.2023.07.004

TY - JOUR

T1 - Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

AU - Chowdhury, Shrabanti

AU - Kennedy, Jacob J.

AU - Ivey, Richard G.

AU - Murillo, Oscar D.

AU - Hosseini, Noshad

AU - Song, Xiaoyu

AU - Petralia, Francesca

AU - Calinawan, Anna

AU - Savage, Sara R.

AU - Berry, Anna B.

AU - Reva, Boris

AU - Ozbek, Umut

AU - Krek, Azra

AU - Ma, Weiping

AU - da Veiga Leprevost, Felipe

AU - Ji, Jiayi

AU - Yoo, Seungyeul

AU - Lin, Chenwei

AU - Voytovich, Uliana J.

AU - Huang, Yajue

AU - Lee, Sun Hee

AU - Bergan, Lindsay

AU - Lorentzen, Travis D.

AU - Mesri, Mehdi

AU - Rodriguez, Henry

AU - Hoofnagle, Andrew N.

AU - Herbert, Zachary T.

AU - Nesvizhskii, Alexey I.

AU - Zhang, Bing

AU - Whiteaker, Jeffrey R.

AU - Fenyo, David

AU - McKerrow, Wilson

AU - Wang, Joshua

AU - Schürer, Stephan C.

AU - Stathias, Vasileios

AU - Chen, X. Steven

AU - Barcellos-Hoff, Mary Helen

AU - Starr, Timothy K.

AU - Winterhoff, Boris J.

AU - Nelson, Andrew C.

AU - Mok, Samuel C.

AU - Kaufmann, Scott H.

AU - Drescher, Charles

AU - Cieslik, Marcin

AU - Wang, Pei

AU - Birrer, Michael J.

AU - Paulovich, Amanda G.

PY - 2023/8/3

Y1 - 2023/8/3

N2 - To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.

AB - To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.

KW - chemorefractory

KW - high-grade serous ovarian cancer

KW - machine learning

KW - mass spectrometry

KW - multiple reaction monitoring

KW - platinum

KW - precision oncology

KW - predictive biomarker

KW - prognostic biomarker

KW - proteogenomic

UR - http://www.scopus.com/inward/record.url?scp=85166598577&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.07.004

DO - 10.1016/j.cell.2023.07.004

M3 - Article

C2 - 37541199

AN - SCOPUS:85166598577

SN - 0092-8674

VL - 186

SP - 3476-3498.e35

JO - Cell

JF - Cell

IS - 16

ER -

Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Abstract

Keywords

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