Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

Nicholas W. Bateman; Tamara Abulez; Anthony R. Soltis; Andrew McPherson; Seongmin Choi; Dale W. Garsed; Ahwan Pandey; Chunqiao Tian; Brian L. Hood; Kelly A. Conrads; Pang Ning Teng; Julie Oliver; Glenn Gist; Dave Mitchell; Tracy J. Litzi; Christopher M. Tarney; Barbara A. Crothers; Paulette Mhawech-Fauceglia; Clifton L. Dalgard; Matthew D. Wilkerson; Mariaelena Pierobon; Emanuel F. Petricoin; Chunhua Yan; Daoud Meerzaman; Clara Bodelon; Nicolas Wentzensen; Jerry S.H. Lee; David G. Huntsman; Sohrab Shah; Craig D. Shriver; Neil T. Phippen; Kathleen M. Darcy; David D.L. Bowtell; Thomas P. Conrads; G. Larry Maxwell; Sasha C. Makohon-Moore; Waleed Barakat; Xijun Zhang; Allison Hunt; Wei Ao; Stacey L. Lytle-Gabbin; Yovanni Casablanca; Chad A. Hamilton; Miranda Newell; Justin Wells; Gauthaman Sukumar; Dagmar Bacikova; John Freyman; David E. Cohn; Andrew Berchuck; Laura Havrilesky; Linda Duska; Adekunle Odunsi; Anil Sood; James Brenton; Evis Sala; Christina Annunziata; Oliver Dorigo; Brad Nelson; Dawn R. Cochrane; Kathleen Moore; Elisa Baldelli; Qing Rong Chen; Ying Hu; Sian Fereday; Nadia Traficante; Anna DeFazio; Ellen L. Goode

doi:10.1038/s41698-024-00519-8

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

Nicholas W. Bateman, Tamara Abulez, Anthony R. Soltis, Andrew McPherson, Seongmin Choi, Dale W. Garsed, Ahwan Pandey, Chunqiao Tian, Brian L. Hood, Kelly A. Conrads, Pang Ning Teng, Julie Oliver, Glenn Gist, Dave Mitchell, Tracy J. Litzi, Christopher M. Tarney, Barbara A. Crothers, Paulette Mhawech-Fauceglia, Clifton L. Dalgard, Matthew D. WilkersonMariaelena Pierobon, Emanuel F. Petricoin, Chunhua Yan, Daoud Meerzaman, Clara Bodelon, Nicolas Wentzensen, Jerry S.H. Lee, David G. Huntsman, Sohrab Shah, Craig D. Shriver, Neil T. Phippen, Kathleen M. Darcy, David D.L. Bowtell, Thomas P. Conrads, G. Larry Maxwell, Sasha C. Makohon-Moore, Waleed Barakat, Xijun Zhang, Allison Hunt, Wei Ao, Stacey L. Lytle-Gabbin, Yovanni Casablanca, Chad A. Hamilton, Miranda Newell, Justin Wells, Gauthaman Sukumar, Dagmar Bacikova, John Freyman, David E. Cohn, Andrew Berchuck, Laura Havrilesky, Linda Duska, Adekunle Odunsi, Anil Sood, James Brenton, Evis Sala, Christina Annunziata, Oliver Dorigo, Brad Nelson, Dawn R. Cochrane, Kathleen Moore, Elisa Baldelli, Qing Rong Chen, Ying Hu, Sian Fereday, Nadia Traficante, Anna DeFazio, Ellen L. Goode

Gynecological Oncology & Reproductive Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

Original language	English (US)
Article number	68
Journal	npj Precision Oncology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41698-024-00519-8
State	Published - Dec 2024

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/s41698-024-00519-8

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Bateman, N. W., Abulez, T., Soltis, A. R., McPherson, A., Choi, S., Garsed, D. W., Pandey, A., Tian, C., Hood, B. L., Conrads, K. A., Teng, P. N., Oliver, J., Gist, G., Mitchell, D., Litzi, T. J., Tarney, C. M., Crothers, B. A., Mhawech-Fauceglia, P., Dalgard, C. L., ... Goode, E. L. (2024). Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities. npj Precision Oncology, 8(1), Article 68. https://doi.org/10.1038/s41698-024-00519-8

Bateman, NW, Abulez, T, Soltis, AR, McPherson, A, Choi, S, Garsed, DW, Pandey, A, Tian, C, Hood, BL, Conrads, KA, Teng, PN, Oliver, J, Gist, G, Mitchell, D, Litzi, TJ, Tarney, CM, Crothers, BA, Mhawech-Fauceglia, P, Dalgard, CL, Wilkerson, MD, Pierobon, M, Petricoin, EF, Yan, C, Meerzaman, D, Bodelon, C, Wentzensen, N, Lee, JSH, Huntsman, DG, Shah, S, Shriver, CD, Phippen, NT, Darcy, KM, Bowtell, DDL, Conrads, TP, Maxwell, GL, Makohon-Moore, SC, Barakat, W, Zhang, X, Hunt, A, Ao, W, Lytle-Gabbin, SL, Casablanca, Y, Hamilton, CA, Newell, M, Wells, J, Sukumar, G, Bacikova, D, Freyman, J, Cohn, DE, Berchuck, A, Havrilesky, L, Duska, L, Odunsi, A, Sood, A, Brenton, J, Sala, E, Annunziata, C, Dorigo, O, Nelson, B, Cochrane, DR, Moore, K, Baldelli, E, Chen, QR, Hu, Y, Fereday, S, Traficante, N, DeFazio, A & Goode, EL 2024, 'Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities', npj Precision Oncology, vol. 8, no. 1, 68. https://doi.org/10.1038/s41698-024-00519-8

@article{4c11deba19eb4d0ea128aa6b30dcd7ed,

title = "Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities",

abstract = "We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.",

author = "Bateman, {Nicholas W.} and Tamara Abulez and Soltis, {Anthony R.} and Andrew McPherson and Seongmin Choi and Garsed, {Dale W.} and Ahwan Pandey and Chunqiao Tian and Hood, {Brian L.} and Conrads, {Kelly A.} and Teng, {Pang Ning} and Julie Oliver and Glenn Gist and Dave Mitchell and Litzi, {Tracy J.} and Tarney, {Christopher M.} and Crothers, {Barbara A.} and Paulette Mhawech-Fauceglia and Dalgard, {Clifton L.} and Wilkerson, {Matthew D.} and Mariaelena Pierobon and Petricoin, {Emanuel F.} and Chunhua Yan and Daoud Meerzaman and Clara Bodelon and Nicolas Wentzensen and Lee, {Jerry S.H.} and Huntsman, {David G.} and Sohrab Shah and Shriver, {Craig D.} and Phippen, {Neil T.} and Darcy, {Kathleen M.} and Bowtell, {David D.L.} and Conrads, {Thomas P.} and Maxwell, {G. Larry} and Makohon-Moore, {Sasha C.} and Waleed Barakat and Xijun Zhang and Allison Hunt and Wei Ao and Lytle-Gabbin, {Stacey L.} and Yovanni Casablanca and Hamilton, {Chad A.} and Miranda Newell and Justin Wells and Gauthaman Sukumar and Dagmar Bacikova and John Freyman and Cohn, {David E.} and Andrew Berchuck and Laura Havrilesky and Linda Duska and Adekunle Odunsi and Anil Sood and James Brenton and Evis Sala and Christina Annunziata and Oliver Dorigo and Brad Nelson and Cochrane, {Dawn R.} and Kathleen Moore and Elisa Baldelli and Chen, {Qing Rong} and Ying Hu and Sian Fereday and Nadia Traficante and Anna DeFazio and Goode, {Ellen L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41698-024-00519-8",

language = "English (US)",

volume = "8",

journal = "npj Precision Oncology",

issn = "2397-768X",

publisher = "Springer Nature",

number = "1",

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TY - JOUR

T1 - Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

AU - Bateman, Nicholas W.

AU - Abulez, Tamara

AU - Soltis, Anthony R.

AU - McPherson, Andrew

AU - Choi, Seongmin

AU - Garsed, Dale W.

AU - Pandey, Ahwan

AU - Tian, Chunqiao

AU - Hood, Brian L.

AU - Conrads, Kelly A.

AU - Teng, Pang Ning

AU - Oliver, Julie

AU - Gist, Glenn

AU - Mitchell, Dave

AU - Litzi, Tracy J.

AU - Tarney, Christopher M.

AU - Crothers, Barbara A.

AU - Mhawech-Fauceglia, Paulette

AU - Dalgard, Clifton L.

AU - Wilkerson, Matthew D.

AU - Pierobon, Mariaelena

AU - Petricoin, Emanuel F.

AU - Yan, Chunhua

AU - Meerzaman, Daoud

AU - Bodelon, Clara

AU - Wentzensen, Nicolas

AU - Lee, Jerry S.H.

AU - Huntsman, David G.

AU - Shah, Sohrab

AU - Shriver, Craig D.

AU - Phippen, Neil T.

AU - Darcy, Kathleen M.

AU - Bowtell, David D.L.

AU - Conrads, Thomas P.

AU - Maxwell, G. Larry

AU - Makohon-Moore, Sasha C.

AU - Barakat, Waleed

AU - Zhang, Xijun

AU - Hunt, Allison

AU - Ao, Wei

AU - Lytle-Gabbin, Stacey L.

AU - Casablanca, Yovanni

AU - Hamilton, Chad A.

AU - Newell, Miranda

AU - Wells, Justin

AU - Sukumar, Gauthaman

AU - Bacikova, Dagmar

AU - Freyman, John

AU - Cohn, David E.

AU - Berchuck, Andrew

AU - Havrilesky, Laura

AU - Duska, Linda

AU - Odunsi, Adekunle

AU - Sood, Anil

AU - Brenton, James

AU - Sala, Evis

AU - Annunziata, Christina

AU - Dorigo, Oliver

AU - Nelson, Brad

AU - Cochrane, Dawn R.

AU - Moore, Kathleen

AU - Baldelli, Elisa

AU - Chen, Qing Rong

AU - Hu, Ying

AU - Fereday, Sian

AU - Traficante, Nadia

AU - DeFazio, Anna

AU - Goode, Ellen L.

PY - 2024/12

Y1 - 2024/12

N2 - We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

AB - We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

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U2 - 10.1038/s41698-024-00519-8

DO - 10.1038/s41698-024-00519-8

M3 - Article

C2 - 38480868

AN - SCOPUS:85187713482

SN - 2397-768X

VL - 8

JO - npj Precision Oncology

JF - npj Precision Oncology

IS - 1

M1 - 68

ER -

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

Abstract

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