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The phosphoproteome of ovarian carcinoma delineates signaling signatures and potentially druggable targets across histotype stages

Werner, Lucas ; Esmaeili, Parisa LU orcid ; Ittner, Ella ; Swenson, Hugo ; Kovács, Anikó ; Mateoiu, Claudia ; Dahm-Kähler, Pernilla ; Karlsson, Per ; Parris, Toshima and Levander, Fredrik LU orcid , et al. (2026) In NPJ precision oncology 10(1).
Abstract

Ovarian malignancy is the most lethal gynecologic tumor, with an 80% relapse rate and 47% five-year survival. Epithelial ovarian cancer (EOC), the most common form, comprises five major histotypes with distinct clinicopathological characteristics, yet treatment still relies largely on cytoreductive surgery and platinum-based chemotherapy. Phosphoproteomics enables the mapping of protein phosphorylation, a key hallmark of cellular signaling. This study aimed to define phosphoproteomic-based ovarian cancer subgroups and assess their relationships with pathway activation patterns, patient prognosis, and therapeutic relevance. We analyzed the phosphoproteome of four major EOC histotypes from 180 patients. Dysregulated phosphosites critical... (More)

Ovarian malignancy is the most lethal gynecologic tumor, with an 80% relapse rate and 47% five-year survival. Epithelial ovarian cancer (EOC), the most common form, comprises five major histotypes with distinct clinicopathological characteristics, yet treatment still relies largely on cytoreductive surgery and platinum-based chemotherapy. Phosphoproteomics enables the mapping of protein phosphorylation, a key hallmark of cellular signaling. This study aimed to define phosphoproteomic-based ovarian cancer subgroups and assess their relationships with pathway activation patterns, patient prognosis, and therapeutic relevance. We analyzed the phosphoproteome of four major EOC histotypes from 180 patients. Dysregulated phosphosites critical for carcinogenesis were identified, including NUCKS1:S181, WWTR1:S89, and SRRM2:T1880. Kinase activity revealed histotype-specific CDK1/2 signatures linked to EOC-related signaling pathways. Prognostic phosphosites displayed stage- and histotype-dependent patterns. Collectively, these findings elucidate signaling cascades driving disease progression and identify potential therapeutic targets in early and advanced EOC, supporting future efforts toward the development of histotype-specific treatment strategies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NPJ precision oncology
volume
10
issue
1
article number
317
publisher
Springer Nature
external identifiers
  • pmid:42601376
  • scopus:105047451420
ISSN
2397-768X
DOI
10.1038/s41698-026-01659-9
language
English
LU publication?
yes
id
690a8a4d-5df6-4b63-ad3a-2802fb8a6e8f
date added to LUP
2026-09-10 15:54:46
date last changed
2026-09-11 03:25:11
@article{690a8a4d-5df6-4b63-ad3a-2802fb8a6e8f,
  abstract     = {{<p>Ovarian malignancy is the most lethal gynecologic tumor, with an 80% relapse rate and 47% five-year survival. Epithelial ovarian cancer (EOC), the most common form, comprises five major histotypes with distinct clinicopathological characteristics, yet treatment still relies largely on cytoreductive surgery and platinum-based chemotherapy. Phosphoproteomics enables the mapping of protein phosphorylation, a key hallmark of cellular signaling. This study aimed to define phosphoproteomic-based ovarian cancer subgroups and assess their relationships with pathway activation patterns, patient prognosis, and therapeutic relevance. We analyzed the phosphoproteome of four major EOC histotypes from 180 patients. Dysregulated phosphosites critical for carcinogenesis were identified, including NUCKS1:S181, WWTR1:S89, and SRRM2:T1880. Kinase activity revealed histotype-specific CDK1/2 signatures linked to EOC-related signaling pathways. Prognostic phosphosites displayed stage- and histotype-dependent patterns. Collectively, these findings elucidate signaling cascades driving disease progression and identify potential therapeutic targets in early and advanced EOC, supporting future efforts toward the development of histotype-specific treatment strategies.</p>}},
  author       = {{Werner, Lucas and Esmaeili, Parisa and Ittner, Ella and Swenson, Hugo and Kovács, Anikó and Mateoiu, Claudia and Dahm-Kähler, Pernilla and Karlsson, Per and Parris, Toshima and Levander, Fredrik and Helou, Khalil}},
  issn         = {{2397-768X}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{NPJ precision oncology}},
  title        = {{The phosphoproteome of ovarian carcinoma delineates signaling signatures and potentially druggable targets across histotype stages}},
  url          = {{http://dx.doi.org/10.1038/s41698-026-01659-9}},
  doi          = {{10.1038/s41698-026-01659-9}},
  volume       = {{10}},
  year         = {{2026}},
}