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Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling.
Hunt, Allison L; Bateman, Nicholas W; Barakat, Waleed; Makohon-Moore, Sasha C; Abulez, Tamara; Driscoll, Jordan A; Schaaf, Joshua P; Hood, Brian L; Conrads, Kelly A; Zhou, Ming; Calvert, Valerie; Pierobon, Mariaelena; Loffredo, Jeremy; Wilson, Katlin N; Litzi, Tracy J; Teng, Pang-Ning; Oliver, Julie; Mitchell, Dave; Gist, Glenn; Rojas, Christine; Blanton, Brian; Darcy, Kathleen M; Rao, Uma N M; Petricoin, Emanuel F; Phippen, Neil T; Maxwell, G Larry; Conrads, Thomas P.
Affiliation
  • Hunt AL; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Rd, Suite 375, Annandale, VA, 22042, USA.
  • Bateman NW; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Barakat W; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Makohon-Moore SC; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Abulez T; Department of Surgery, The John P. Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Driscoll JA; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Schaaf JP; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Hood BL; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Conrads KA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Zhou M; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Calvert V; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Pierobon M; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Loffredo J; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Wilson KN; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Litzi TJ; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Teng PN; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Oliver J; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Mitchell D; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Gist G; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Rojas C; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Rd, Suite 375, Annandale, VA, 22042, USA.
  • Blanton B; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Darcy KM; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
  • Rao UNM; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
  • Petricoin EF; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Phippen NT; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Maxwell GL; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Conrads TP; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
Clin Proteomics ; 21(1): 4, 2024 Jan 22.
Article in En | MEDLINE | ID: mdl-38254014
ABSTRACT

BACKGROUND:

Although uterine serous carcinoma (USC) represents a small proportion of all uterine cancer cases, patients with this aggressive subtype typically have high rates of chemotherapy resistance and disease recurrence that collectively result in a disproportionately high death rate. The goal of this study was to provide a deeper view of the tumor microenvironment of this poorly characterized uterine cancer variant through multi-region microsampling and quantitative proteomics.

METHODS:

Tumor epithelium, tumor-involved stroma, and whole "bulk" tissue were harvested by laser microdissection (LMD) from spatially resolved levels from nine USC patient tumor specimens and underwent proteomic analysis by mass spectrometry and reverse phase protein arrays, as well as transcriptomic analysis by RNA-sequencing for one patient's tumor.

RESULTS:

LMD enriched cell subpopulations demonstrated varying degrees of relatedness, indicating substantial intratumor heterogeneity emphasizing the necessity for enrichment of cellular subpopulations prior to molecular analysis. Known prognostic biomarkers were quantified with stable levels in both LMD enriched tumor and stroma, which were shown to be highly variable in bulk tissue. These USC data were further used in a comparative analysis with a data generated from another serous gynecologic malignancy, high grade serous ovarian carcinoma, and have been added to our publicly available data analysis tool, the Heterogeneity Analysis Portal ( https//lmdomics.org/ ).

CONCLUSIONS:

Here we identified extensive three-dimensional heterogeneity within the USC tumor microenvironment, with disease-relevant biomarkers present in both the tumor and the stroma. These data underscore the critical need for upfront enrichment of cellular subpopulations from tissue specimens for spatial proteogenomic analysis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Clin Proteomics Year: 2024 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Clin Proteomics Year: 2024 Document type: Article Affiliation country: Country of publication: