Quantitative proteomics identifies conserved proteins and altered regulation of mucin-16 in low grade serous ovarian cancers

Christopher M Tarney ^1,2, Paulette Mhawech-Fauceglia ¹, Jonathan D Ogata ^1,3

¹Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA.
²The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, 20889, MD, USA.
³Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, 20817, MD, USA.
⁴Joint Pathology Center, Silver Spring, 20910, MD, USA.
⁵Department of Pathology and Laboratory Medicine, Inova Health System, Falls church, 22003, VA, USA.
⁶Department of Gynecologic Surgery and Obstetrics, Madigan Army Medical Center, Joint Base Lewis-McChord, Tacoma, 98431, WA, USA.
⁷Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁸Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁹Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Rd, Suite 375, Annandale, 22003, VA, USA.
¹⁰Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA. conrads@whirc.org.
¹¹The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, 20889, MD, USA. conrads@whirc.org.
¹²Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Rd, Suite 375, Annandale, 22003, VA, USA. conrads@whirc.org.
¹³Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA. batemann@whirc.org.
¹⁴The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, 20889, MD, USA. batemann@whirc.org.
¹⁵Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, 20817, MD, USA. batemann@whirc.org.

⁰Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA.

Clinical Proteomics +

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October 6, 2025

View abstract on PubMed

Summary

This study reveals conserved proteome alterations in low-grade serous ovarian carcinoma (LGSOC), identifying CD73 as a potential drug target and MUC16 (CA125) as elevated with unique staining in LGSOC tumors.

Area Of Science

Oncology
Proteomics
Molecular Biology

Background

Low-grade serous ovarian carcinoma (LGSOC) is a rare, chemoresistant ovarian cancer subtype with limited treatment options.
Lack of deep molecular characterization hinders effective management strategies for LGSOC patients.
Existing treatments primarily focus on high-grade serous ovarian cancer (HGSOC), necessitating distinct LGSOC research.

Purpose Of The Study

To define conserved proteome alterations in LGSOC through deep quantitative proteomic analysis.
To validate identified protein alterations in independent LGSOC and HGSOC tumor datasets.
To identify potential therapeutic targets and understand molecular differences between LGSOC and HGSOC.

Main Methods

Quantitative proteomic analysis of LGSOC, HGSOC, and normal fallopian tube tissues using TMT11 workflow and mass spectrometry.
Validation of proteome alterations using two independent proteomic datasets of LGSOC and HGSOC tumors.
Immunohistochemistry to assess Mucin-16 (MUC16/CA125) expression and localization in LGSOC and HGSOC tumors.

Main Results

Identified 275 conserved protein alterations between LGSOC and HGSOC with high correlation (Spearman Rho ≥ 0.82).
Conserved proteins elevated in LGSOC are linked to cell adhesion and apoptosis pathways; CD73 (NT5E) identified as a putative drug target.
MUC16 (CA125) was significantly elevated in LGSOC versus HGSOC, with a distinct apical staining pattern observed in LGSOC tumors.

Conclusions

Defined highly conserved protein alterations distinguishing LGSOC from HGSOC, including CD73.
Novelly identified elevated MUC16 (CA125) with an apical staining pattern in LGSOC tumor tissues.
Provided deeper molecular understanding of LGSOC and insights into its conserved proteome alterations.

Keywords:

5'-nucleotidase CA125 CD73 Cancer antigen 125 Cluster of differentiation 73 HGSOC High-grade serous ovarian cancer LGSOC Low-grade serous ovarian cancer MUC16 Mucin-16 NT5E Quantitative proteomics

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