Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma

Gerardo Velez; Harvey Pass; Michele Carbone; Haining Yang; Chandra Goparaju

doi:doi:10.11648/j.crj.20210901.18

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Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma

Gerardo Velez, Harvey Pass, Michele Carbone, Haining Yang, Chandra Goparaju

Published in Cancer Research Journal (Volume 9, Issue 1)

Received: 16 February 2021 Accepted: 5 March 2021 Published: 12 March 2021

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Abstract

Malignant pleural mesothelioma is a highly aggressive tumor primarily caused by asbestos exposure and associated with poor clinical outcomes. The availability of a robust non-invasive test for the screening of asbestos-exposed subjects is therefore an important unmet clinical need. It is widely recognized that the immune system can play a fundamental role in the control of tumor growth within an organism. Simultaneously, the presence of cancer cells can activate different immune cells to undergo various phenotypic and functional changes. Buffy coat—a novel circulating microenvironment of leukocytes and platelets—may thus reflect critical immuno-oncologic activity, pathways, and molecular programs. We hypothesized the immunotranscriptome of circulating buffy coat could accurately distinguish malignant pleural mesothelioma from high-risk asbestos exposure. Buffy coat RNA was extracted from 84 patients having resection: 40 patients with malignant pleural mesothelioma and 44 patients with asbestos exposure. Gene expression profiling was performed using a Pan Cancer Immune Panel for 770 immune genes and cytokines, and significantly different genes between cohorts were selected to develop diagnostic models. Using 1000 loops of cross validation, a 37 gene signature separated malignant pleural mesothelioma from asbestos exposure with a mean validation AUCS of 0.925. Our buffy coat immunotranscriptomic signature is at least comparable to the most commonly used blood-based diagnostic biomarker for MPM, serum mesothelin-related peptide. In addition, immunophenotyping and pathway analysis of differentially expressed genes characterized MPM buffy coat as a relatively tumorigenic and immunosuppressive state. Several of the most differentially expressed genes encode proteins implicated in cancer development (e.g., CD63, CD44, ISG15, CD59, IL1R2, and TAPBP) and may hold clinical value as therapeutic targets. Larger studies on externally validated cohorts are needed to refine the signature for clinical relevance and develop a more robust diagnostic panel.

Published in	Cancer Research Journal (Volume 9, Issue 1)
DOI	10.11648/j.crj.20210901.18
Page(s)	61-70
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Mesothelioma, Asbestos, Buffy Coat, Transcriptomics, Gene Expression, Biomarker, Liquid Biopsy

References

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APA Style

Gerardo Velez, Harvey Pass, Michele Carbone, Haining Yang, Chandra Goparaju. (2021). Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Research Journal, 9(1), 61-70. https://doi.org/10.11648/j.crj.20210901.18

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ACS Style

Gerardo Velez; Harvey Pass; Michele Carbone; Haining Yang; Chandra Goparaju. Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Res. J. 2021, 9(1), 61-70. doi: 10.11648/j.crj.20210901.18

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AMA Style

Gerardo Velez, Harvey Pass, Michele Carbone, Haining Yang, Chandra Goparaju. Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Res J. 2021;9(1):61-70. doi: 10.11648/j.crj.20210901.18

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@article{10.11648/j.crj.20210901.18,
  author = {Gerardo Velez and Harvey Pass and Michele Carbone and Haining Yang and Chandra Goparaju},
  title = {Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma},
  journal = {Cancer Research Journal},
  volume = {9},
  number = {1},
  pages = {61-70},
  doi = {10.11648/j.crj.20210901.18},
  url = {https://doi.org/10.11648/j.crj.20210901.18},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20210901.18},
  abstract = {Malignant pleural mesothelioma is a highly aggressive tumor primarily caused by asbestos exposure and associated with poor clinical outcomes. The availability of a robust non-invasive test for the screening of asbestos-exposed subjects is therefore an important unmet clinical need. It is widely recognized that the immune system can play a fundamental role in the control of tumor growth within an organism. Simultaneously, the presence of cancer cells can activate different immune cells to undergo various phenotypic and functional changes. Buffy coat—a novel circulating microenvironment of leukocytes and platelets—may thus reflect critical immuno-oncologic activity, pathways, and molecular programs. We hypothesized the immunotranscriptome of circulating buffy coat could accurately distinguish malignant pleural mesothelioma from high-risk asbestos exposure. Buffy coat RNA was extracted from 84 patients having resection: 40 patients with malignant pleural mesothelioma and 44 patients with asbestos exposure. Gene expression profiling was performed using a Pan Cancer Immune Panel for 770 immune genes and cytokines, and significantly different genes between cohorts were selected to develop diagnostic models. Using 1000 loops of cross validation, a 37 gene signature separated malignant pleural mesothelioma from asbestos exposure with a mean validation AUCS of 0.925. Our buffy coat immunotranscriptomic signature is at least comparable to the most commonly used blood-based diagnostic biomarker for MPM, serum mesothelin-related peptide. In addition, immunophenotyping and pathway analysis of differentially expressed genes characterized MPM buffy coat as a relatively tumorigenic and immunosuppressive state. Several of the most differentially expressed genes encode proteins implicated in cancer development (e.g., CD63, CD44, ISG15, CD59, IL1R2, and TAPBP) and may hold clinical value as therapeutic targets. Larger studies on externally validated cohorts are needed to refine the signature for clinical relevance and develop a more robust diagnostic panel.},
 year = {2021}
}

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TY  - JOUR
T1  - Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma
AU  - Gerardo Velez
AU  - Harvey Pass
AU  - Michele Carbone
AU  - Haining Yang
AU  - Chandra Goparaju
Y1  - 2021/03/12
PY  - 2021
N1  - https://doi.org/10.11648/j.crj.20210901.18
DO  - 10.11648/j.crj.20210901.18
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 61
EP  - 70
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20210901.18
AB  - Malignant pleural mesothelioma is a highly aggressive tumor primarily caused by asbestos exposure and associated with poor clinical outcomes. The availability of a robust non-invasive test for the screening of asbestos-exposed subjects is therefore an important unmet clinical need. It is widely recognized that the immune system can play a fundamental role in the control of tumor growth within an organism. Simultaneously, the presence of cancer cells can activate different immune cells to undergo various phenotypic and functional changes. Buffy coat—a novel circulating microenvironment of leukocytes and platelets—may thus reflect critical immuno-oncologic activity, pathways, and molecular programs. We hypothesized the immunotranscriptome of circulating buffy coat could accurately distinguish malignant pleural mesothelioma from high-risk asbestos exposure. Buffy coat RNA was extracted from 84 patients having resection: 40 patients with malignant pleural mesothelioma and 44 patients with asbestos exposure. Gene expression profiling was performed using a Pan Cancer Immune Panel for 770 immune genes and cytokines, and significantly different genes between cohorts were selected to develop diagnostic models. Using 1000 loops of cross validation, a 37 gene signature separated malignant pleural mesothelioma from asbestos exposure with a mean validation AUCS of 0.925. Our buffy coat immunotranscriptomic signature is at least comparable to the most commonly used blood-based diagnostic biomarker for MPM, serum mesothelin-related peptide. In addition, immunophenotyping and pathway analysis of differentially expressed genes characterized MPM buffy coat as a relatively tumorigenic and immunosuppressive state. Several of the most differentially expressed genes encode proteins implicated in cancer development (e.g., CD63, CD44, ISG15, CD59, IL1R2, and TAPBP) and may hold clinical value as therapeutic targets. Larger studies on externally validated cohorts are needed to refine the signature for clinical relevance and develop a more robust diagnostic panel.
VL  - 9
IS  - 1
ER  -

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Author Information

Gerardo Velez

Department of Cardiothoracic Surgery, NYU Langone Health, New York, USA
Harvey Pass

Department of Cardiothoracic Surgery, NYU Langone Health, New York, USA
Michele Carbone

Department of Cardiothoracic Surgery, NYU Langone Health, New York, USA
Haining Yang

Department of Cardiothoracic Surgery, NYU Langone Health, New York, USA
Chandra Goparaju

Department of Cardiothoracic Surgery, NYU Langone Health, New York, USA

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APA Style

Gerardo Velez, Harvey Pass, Michele Carbone, Haining Yang, Chandra Goparaju. (2021). Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Research Journal, 9(1), 61-70. https://doi.org/10.11648/j.crj.20210901.18

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ACS Style

Gerardo Velez; Harvey Pass; Michele Carbone; Haining Yang; Chandra Goparaju. Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Res. J. 2021, 9(1), 61-70. doi: 10.11648/j.crj.20210901.18

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AMA Style

Gerardo Velez, Harvey Pass, Michele Carbone, Haining Yang, Chandra Goparaju. Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma. Cancer Res J. 2021;9(1):61-70. doi: 10.11648/j.crj.20210901.18

Copy | Download

@article{10.11648/j.crj.20210901.18,
  author = {Gerardo Velez and Harvey Pass and Michele Carbone and Haining Yang and Chandra Goparaju},
  title = {Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma},
  journal = {Cancer Research Journal},
  volume = {9},
  number = {1},
  pages = {61-70},
  doi = {10.11648/j.crj.20210901.18},
  url = {https://doi.org/10.11648/j.crj.20210901.18},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20210901.18},
  abstract = {Malignant pleural mesothelioma is a highly aggressive tumor primarily caused by asbestos exposure and associated with poor clinical outcomes. The availability of a robust non-invasive test for the screening of asbestos-exposed subjects is therefore an important unmet clinical need. It is widely recognized that the immune system can play a fundamental role in the control of tumor growth within an organism. Simultaneously, the presence of cancer cells can activate different immune cells to undergo various phenotypic and functional changes. Buffy coat—a novel circulating microenvironment of leukocytes and platelets—may thus reflect critical immuno-oncologic activity, pathways, and molecular programs. We hypothesized the immunotranscriptome of circulating buffy coat could accurately distinguish malignant pleural mesothelioma from high-risk asbestos exposure. Buffy coat RNA was extracted from 84 patients having resection: 40 patients with malignant pleural mesothelioma and 44 patients with asbestos exposure. Gene expression profiling was performed using a Pan Cancer Immune Panel for 770 immune genes and cytokines, and significantly different genes between cohorts were selected to develop diagnostic models. Using 1000 loops of cross validation, a 37 gene signature separated malignant pleural mesothelioma from asbestos exposure with a mean validation AUCS of 0.925. Our buffy coat immunotranscriptomic signature is at least comparable to the most commonly used blood-based diagnostic biomarker for MPM, serum mesothelin-related peptide. In addition, immunophenotyping and pathway analysis of differentially expressed genes characterized MPM buffy coat as a relatively tumorigenic and immunosuppressive state. Several of the most differentially expressed genes encode proteins implicated in cancer development (e.g., CD63, CD44, ISG15, CD59, IL1R2, and TAPBP) and may hold clinical value as therapeutic targets. Larger studies on externally validated cohorts are needed to refine the signature for clinical relevance and develop a more robust diagnostic panel.},
 year = {2021}
}

Copy | Download

TY  - JOUR
T1  - Buffy Coat Immunotranscriptomics for Diagnosis of Malignant Pleural Mesothelioma
AU  - Gerardo Velez
AU  - Harvey Pass
AU  - Michele Carbone
AU  - Haining Yang
AU  - Chandra Goparaju
Y1  - 2021/03/12
PY  - 2021
N1  - https://doi.org/10.11648/j.crj.20210901.18
DO  - 10.11648/j.crj.20210901.18
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 61
EP  - 70
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20210901.18
AB  - Malignant pleural mesothelioma is a highly aggressive tumor primarily caused by asbestos exposure and associated with poor clinical outcomes. The availability of a robust non-invasive test for the screening of asbestos-exposed subjects is therefore an important unmet clinical need. It is widely recognized that the immune system can play a fundamental role in the control of tumor growth within an organism. Simultaneously, the presence of cancer cells can activate different immune cells to undergo various phenotypic and functional changes. Buffy coat—a novel circulating microenvironment of leukocytes and platelets—may thus reflect critical immuno-oncologic activity, pathways, and molecular programs. We hypothesized the immunotranscriptome of circulating buffy coat could accurately distinguish malignant pleural mesothelioma from high-risk asbestos exposure. Buffy coat RNA was extracted from 84 patients having resection: 40 patients with malignant pleural mesothelioma and 44 patients with asbestos exposure. Gene expression profiling was performed using a Pan Cancer Immune Panel for 770 immune genes and cytokines, and significantly different genes between cohorts were selected to develop diagnostic models. Using 1000 loops of cross validation, a 37 gene signature separated malignant pleural mesothelioma from asbestos exposure with a mean validation AUCS of 0.925. Our buffy coat immunotranscriptomic signature is at least comparable to the most commonly used blood-based diagnostic biomarker for MPM, serum mesothelin-related peptide. In addition, immunophenotyping and pathway analysis of differentially expressed genes characterized MPM buffy coat as a relatively tumorigenic and immunosuppressive state. Several of the most differentially expressed genes encode proteins implicated in cancer development (e.g., CD63, CD44, ISG15, CD59, IL1R2, and TAPBP) and may hold clinical value as therapeutic targets. Larger studies on externally validated cohorts are needed to refine the signature for clinical relevance and develop a more robust diagnostic panel.
VL  - 9
IS  - 1
ER  -

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