Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens
Summary: Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA seq...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221007252 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Allison L. Hunt Nicholas W. Bateman Waleed Barakat Sasha Makohon-Moore Brian L. Hood Kelly A. Conrads Ming Zhou Valerie Calvert Mariaelena Pierobon Jeremy Loffredo Tracy J. Litzi Julie Oliver Dave Mitchell Glenn Gist Christine Rojas Brian Blanton Emma L. Robinson Kunle Odunsi Anil K. Sood Yovanni Casablanca Kathleen M. Darcy Craig D. Shriver Emanuel F. Petricoin Uma N.M. Rao G. Larry Maxwell Thomas P. Conrads |
| spellingShingle |
Allison L. Hunt Nicholas W. Bateman Waleed Barakat Sasha Makohon-Moore Brian L. Hood Kelly A. Conrads Ming Zhou Valerie Calvert Mariaelena Pierobon Jeremy Loffredo Tracy J. Litzi Julie Oliver Dave Mitchell Glenn Gist Christine Rojas Brian Blanton Emma L. Robinson Kunle Odunsi Anil K. Sood Yovanni Casablanca Kathleen M. Darcy Craig D. Shriver Emanuel F. Petricoin Uma N.M. Rao G. Larry Maxwell Thomas P. Conrads Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens iScience Oncology Cancer systems biology Proteomics Transcriptomics |
| author_facet |
Allison L. Hunt Nicholas W. Bateman Waleed Barakat Sasha Makohon-Moore Brian L. Hood Kelly A. Conrads Ming Zhou Valerie Calvert Mariaelena Pierobon Jeremy Loffredo Tracy J. Litzi Julie Oliver Dave Mitchell Glenn Gist Christine Rojas Brian Blanton Emma L. Robinson Kunle Odunsi Anil K. Sood Yovanni Casablanca Kathleen M. Darcy Craig D. Shriver Emanuel F. Petricoin Uma N.M. Rao G. Larry Maxwell Thomas P. Conrads |
| author_sort |
Allison L. Hunt |
| title |
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| title_short |
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| title_full |
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| title_fullStr |
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| title_full_unstemmed |
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| title_sort |
extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2021-07-01 |
| description |
Summary: Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling. |
| topic |
Oncology Cancer systems biology Proteomics Transcriptomics |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004221007252 |
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doaj-21f41dbd23e4460e8c8c8ab699aed5b82021-07-23T04:50:28ZengElsevieriScience2589-00422021-07-01247102757Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimensAllison L. Hunt0Nicholas W. Bateman1Waleed Barakat2Sasha Makohon-Moore3Brian L. Hood4Kelly A. Conrads5Ming Zhou6Valerie Calvert7Mariaelena Pierobon8Jeremy Loffredo9Tracy J. Litzi10Julie Oliver11Dave Mitchell12Glenn Gist13Christine Rojas14Brian Blanton15Emma L. Robinson16Kunle Odunsi17Anil K. Sood18Yovanni Casablanca19Kathleen M. Darcy20Craig D. Shriver21Emanuel F. Petricoin22Uma N.M. Rao23G. Larry Maxwell24Thomas P. Conrads25Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAWomen's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAWomen's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USADepartment of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USAThe John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USAGynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USAWomen's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Corresponding authorWomen's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Corresponding authorSummary: Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling.http://www.sciencedirect.com/science/article/pii/S2589004221007252OncologyCancer systems biologyProteomicsTranscriptomics |