# Proteomic analysis of ovarian carcinoma reveals diagnostic and prognostic biomarkers with histotype- and stage-specificity

**Authors:** Lucas Werner, Ella Ittner, Hugo Swenson, Elisabeth Werner Rönnerman, Claudia Mateoiu, Anikó Kovács, Pernilla Dahm-Kähler, Per Karlsson, Toshima Z. Parris, Khalil Helou

PMC · DOI: 10.1186/s13048-026-01984-4 · 2026-01-28

## TL;DR

This study identifies proteins specific to different types and stages of ovarian cancer, which could improve diagnosis and treatment.

## Contribution

The study identifies histotype- and stage-specific diagnostic and prognostic biomarkers in epithelial ovarian cancer.

## Key findings

- DAPs like S100A1, AGR2, and CTH are identified without stage-specificity across histotypes.
- Proteins such as TSPYL, VWA2, and GPC6 show stage-specificity for each histotype.
- Proteins like EXO3CL2 and PPIL6 are linked to survival outcomes in specific histotypes and stages.

## Abstract

Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer, due to asymptomatic early stages, vague symptoms in later stages, and limited clinical tools. Despite distinct clinicopathologic features, all EOC histotypes typically receive identical primary treatment, and are often studied as a single entity.

We analyzed the proteome of 244 patients and identified differentially abundant proteins (DAPs) with and without stage specificity across histotypes and constructed panels of DAPs to distinguish histotypes in both early and late stages. Survival analysis was performed to find proteins associated with clinical outcomes, and enrichment analysis was conducted to reveal biological processes connected to prognosis and the proteins involved.

Here we find DAPs without (e.g. S100A1, AGR2, CTH) and with (TSPYL, VWA2, GPC6, S100P) stage-specificity for each histotype. Survival analysis revealed histotype- and stage-specific prognostic markers (e.g., EXO3CL2, PPIL6, GYG1, GAPDH), while biological process enrichment highlighted pathways underlying clinical outcomes.

Our findings provide novel diagnostic and prognostic biomarker candidates and insights into mechanisms driving EOC progression with histotype- and stage-specificity. This may aid the development of improved clinical tools for detection, patient stratification, and targeted therapies in EOC.

The online version contains supplementary material available at 10.1186/s13048-026-01984-4.

## Linked entities

- **Genes:** S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271], AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551], CTH (cystathionine gamma-lyase) [NCBI Gene 1491], TSPYL1 (TSPY like 1) [NCBI Gene 7259], VWA2 (von Willebrand factor A domain containing 2) [NCBI Gene 340706], GPC6 (glypican 6) [NCBI Gene 10082], S100P (S100 calcium binding protein P) [NCBI Gene 6286], PPIL6 (peptidylprolyl isomerase like 6) [NCBI Gene 285755], GYG1 (glycogenin 1) [NCBI Gene 2992], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597]
- **Diseases:** ovarian cancer (MONDO:0005140), epithelial ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551] {aka AG-2, AG2, GOB-4, HAG-2, HEL-S-116, HPC8}, TSPYL1 (TSPY like 1) [NCBI Gene 7259] {aka TSPYL}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, VSIG2 (V-set and immunoglobulin domain containing 2) [NCBI Gene 23584] {aka 2210413P10Rik, CTH, CTXL}, VWA2 (von Willebrand factor A domain containing 2) [NCBI Gene 340706] {aka AMACO, CCSP-2, CCSP2, NET42}, GPC6 (glypican 6) [NCBI Gene 10082] {aka OMIMD1}, S100P (S100 calcium binding protein P) [NCBI Gene 6286] {aka MIG9}, PPIL6 (peptidylprolyl isomerase like 6) [NCBI Gene 285755] {aka PPIase, RSPH12, bA425D10.6, dJ919F19.1}, GYG1 (glycogenin 1) [NCBI Gene 2992] {aka GSD15, GYG}
- **Diseases:** EOC (MESH:D000077216), gynecologic cancer (MESH:D009369), ovarian carcinoma (MESH:D010051)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924536/full.md

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Source: https://tomesphere.com/paper/PMC12924536