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), 2021. Published by Science Publishing Group |
Mesothelioma, Asbestos, Buffy Coat, Transcriptomics, Gene Expression, Biomarker, Liquid Biopsy
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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
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
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
@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} }
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 -