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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Main Authors: Michael S. Parappilly, Yuki Chin, Riley M. Whalen, Ashley N. Anderson, Trinity S. Robinson, Luke Strgar, Thomas L. Sutton, Patrick Conley, Christopher Klocke, Summer L. Gibbs, Young Hwan Chang, Guanming Wu, Melissa H. Wong, Alison H. Skalet
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/14/19/4617
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author Michael S. Parappilly
Yuki Chin
Riley M. Whalen
Ashley N. Anderson
Trinity S. Robinson
Luke Strgar
Thomas L. Sutton
Patrick Conley
Christopher Klocke
Summer L. Gibbs
Young Hwan Chang
Guanming Wu
Melissa H. Wong
Alison H. Skalet
author_facet Michael S. Parappilly
Yuki Chin
Riley M. Whalen
Ashley N. Anderson
Trinity S. Robinson
Luke Strgar
Thomas L. Sutton
Patrick Conley
Christopher Klocke
Summer L. Gibbs
Young Hwan Chang
Guanming Wu
Melissa H. Wong
Alison H. Skalet
author_sort Michael S. Parappilly
collection DOAJ
description 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, <i>n</i> = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (<i>p</i> = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (<i>p</i> < 0.03) and overall survival (<i>p</i> < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.
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spelling doaj.art-e4a07db2af2e40499c108912514781862023-11-23T19:53:44ZengMDPI AGCancers2072-66942022-09-011419461710.3390/cancers14194617Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal MelanomaMichael S. Parappilly0Yuki Chin1Riley M. Whalen2Ashley N. Anderson3Trinity S. Robinson4Luke Strgar5Thomas L. Sutton6Patrick Conley7Christopher Klocke8Summer L. Gibbs9Young Hwan Chang10Guanming Wu11Melissa H. Wong12Alison H. Skalet13Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USADepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USADepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USADepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USADepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97201, USADepartment of Surgery, Oregon Health & Science University, Portland, OR 97239, USADepartment of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97201, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97201, USADepartment of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USAKnight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USABackground: 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, <i>n</i> = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (<i>p</i> = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (<i>p</i> < 0.03) and overall survival (<i>p</i> < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.https://www.mdpi.com/2072-6694/14/19/4617uveal melanomacirculating hybrid cellscancer biomarkercirculating tumor cells
spellingShingle Michael S. Parappilly
Yuki Chin
Riley M. Whalen
Ashley N. Anderson
Trinity S. Robinson
Luke Strgar
Thomas L. Sutton
Patrick Conley
Christopher Klocke
Summer L. Gibbs
Young Hwan Chang
Guanming Wu
Melissa H. Wong
Alison H. Skalet
Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
Cancers
uveal melanoma
circulating hybrid cells
cancer biomarker
circulating tumor cells
title Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
title_full Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
title_fullStr Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
title_full_unstemmed Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
title_short Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
title_sort circulating neoplastic immune hybrid cells predict metastatic progression in uveal melanoma
topic uveal melanoma
circulating hybrid cells
cancer biomarker
circulating tumor cells
url https://www.mdpi.com/2072-6694/14/19/4617
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