Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma

Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologi...

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Published in:	Cancers Vol. 14; no. 19; p. 4617
Main Authors:	Parappilly, Michael S, Chin, Yuki, Whalen, Riley M, Anderson, Ashley N, Robinson, Trinity S, Strgar, Luke, Sutton, Thomas L, Conley, Patrick, Klocke, Christopher, Gibbs, Summer L, Chang, Young Hwan, Wu, Guanming, Wong, Melissa H, Skalet, Alison H
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 23-09-2022 MDPI
Subjects:	Antibodies Antigens Biomarkers Biopsy Cancer Cancer cells Development and progression Disease spread Eye cancer Gene expression Health aspects Immunocytochemistry Melanoma Metastases Metastasis Patients Peripheral blood Population Protein expression Proteins Tumor cells Tumors United States United States > US Germany circulating hybrid cells cancer biomarker circulating tumor cells uveal melanoma
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Abstract	Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.
AbstractList	Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma. Uveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease spreads in nearly half of uveal melanoma patients, and is fatal. We discovered a new tumor cell population in the blood stream of cancer patients that has combined tumor cell and white blood cell features. These cells, called circulating hybrid cells, can develop into metastatic tumors. Recently, we detected circulating hybrid cells in the blood of patients with uveal melanoma. In this study we determine that the number of circulating hybrid cells in the blood at time of initial treatment of uveal melanomas predicts future development of disease spread. Circulating hybrid cells have promise as a non-invasive and repeatable “liquid biopsy” for uveal melanoma patients. Therefore, study of this newly discovered cancer cell will improve understanding of the biology of disease progression in uveal melanoma. Uveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease spreads in nearly half of uveal melanoma patients, and is fatal. We discovered a new tumor cell population in the blood stream of cancer patients that has combined tumor cell and white blood cell features. These cells, called circulating hybrid cells, can develop into metastatic tumors. Recently, we detected circulating hybrid cells in the blood of patients with uveal melanoma. In this study we determine that the number of circulating hybrid cells in the blood at time of initial treatment of uveal melanomas predicts future development of disease spread. Circulating hybrid cells have promise as a non-invasive and repeatable “liquid biopsy” for uveal melanoma patients. Therefore, study of this newly discovered cancer cell will improve understanding of the biology of disease progression in uveal melanoma. Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma. Simple SummaryUveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease spreads in nearly half of uveal melanoma patients, and is fatal. We discovered a new tumor cell population in the blood stream of cancer patients that has combined tumor cell and white blood cell features. These cells, called circulating hybrid cells, can develop into metastatic tumors. Recently, we detected circulating hybrid cells in the blood of patients with uveal melanoma. In this study we determine that the number of circulating hybrid cells in the blood at time of initial treatment of uveal melanomas predicts future development of disease spread. Circulating hybrid cells have promise as a non-invasive and repeatable “liquid biopsy” for uveal melanoma patients. Therefore, study of this newly discovered cancer cell will improve understanding of the biology of disease progression in uveal melanoma.AbstractBackground: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.
Audience	Academic
Author	Anderson, Ashley N Wu, Guanming Chin, Yuki Sutton, Thomas L Wong, Melissa H Conley, Patrick Gibbs, Summer L Robinson, Trinity S Strgar, Luke Skalet, Alison H Whalen, Riley M Chang, Young Hwan Klocke, Christopher Parappilly, Michael S
AuthorAffiliation	7 Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA 4 Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA 1 Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA 6 Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA 2 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97201, USA 3 Department of Computational Biology, Oregon Health & Science University, Portland, OR 97239, USA 5 Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA
AuthorAffiliation_xml	– name: 4 Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA – name: 2 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97201, USA – name: 3 Department of Computational Biology, Oregon Health & Science University, Portland, OR 97239, USA – name: 7 Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA – name: 1 Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – name: 6 Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA – name: 5 Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA
Author_xml	– sequence: 1 givenname: Michael S surname: Parappilly fullname: Parappilly, Michael S organization: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 2 givenname: Yuki orcidid: 0000-0001-5328-472X surname: Chin fullname: Chin, Yuki organization: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 3 givenname: Riley M orcidid: 0000-0002-5200-0745 surname: Whalen fullname: Whalen, Riley M organization: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 4 givenname: Ashley N orcidid: 0000-0002-7522-846X surname: Anderson fullname: Anderson, Ashley N organization: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 5 givenname: Trinity S surname: Robinson fullname: Robinson, Trinity S organization: Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 6 givenname: Luke surname: Strgar fullname: Strgar, Luke organization: Department of Computational Biology, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 7 givenname: Thomas L orcidid: 0000-0002-2894-7154 surname: Sutton fullname: Sutton, Thomas L organization: Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 8 givenname: Patrick surname: Conley fullname: Conley, Patrick organization: Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 9 givenname: Christopher surname: Klocke fullname: Klocke, Christopher organization: Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 10 givenname: Summer L surname: Gibbs fullname: Gibbs, Summer L organization: Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 11 givenname: Young Hwan orcidid: 0000-0001-8764-1959 surname: Chang fullname: Chang, Young Hwan organization: Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 12 givenname: Guanming surname: Wu fullname: Wu, Guanming organization: Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 13 givenname: Melissa H orcidid: 0000-0002-5127-279X surname: Wong fullname: Wong, Melissa H organization: Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA – sequence: 14 givenname: Alison H surname: Skalet fullname: Skalet, Alison H organization: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA
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Keywords	circulating hybrid cells cancer biomarker circulating tumor cells uveal melanoma
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Snippet	Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses... Uveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease spreads in nearly... Simple SummaryUveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease...
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SubjectTerms	Antibodies Antigens Biomarkers Biopsy Cancer Cancer cells Development and progression Disease spread Eye cancer Gene expression Health aspects Immunocytochemistry Melanoma Metastases Metastasis Patients Peripheral blood Population Protein expression Proteins Tumor cells Tumors
Title	Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
URI	https://www.ncbi.nlm.nih.gov/pubmed/36230539 https://www.proquest.com/docview/2724229888 https://search.proquest.com/docview/2725197085 https://pubmed.ncbi.nlm.nih.gov/PMC9564048
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