Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes

Snijesh, VP and Nimbalkar, VP and Patil, S and Rajarajan, S and Anupama, CE and Mahalakshmi, S and Alexander, A and Soundharya, R and Ramesh, R and Srinath, BS and Jolly, MK and Prabhu, JS (2024) Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes. In: Translational Oncology, 45 .

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Abstract

Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. Methods: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition (EMT) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort. Results: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis. Conclusion: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes. © 2024

Item Type:	Journal Article
Publication:	Translational Oncology
Publisher:	Neoplasia Press, Inc.
Additional Information:	The copyright for this article belongs to authors.
Keywords:	dexamethasone; glucocorticoid receptor, adult; Article; bioinformatics; cell proliferation; cohort analysis; controlled study; disease free survival; epithelial mesenchymal transition; female; histopathology; human; human tissue; immunocompetent cell; immunohistochemistry; major clinical study; middle aged; protein expression; regulatory T lymphocyte; RNA sequence; single cell RNA seq; stroma cell; triple negative breast cancer; tumor associated leukocyte; tumor cell; tumor microenvironment
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Physical & Mathematical Sciences > Mathematics
Date Deposited:	17 May 2024 09:07
Last Modified:	17 May 2024 09:07
URI:	https://eprints.iisc.ac.in/id/eprint/84740

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