IMR Press / FBL / Volume 26 / Issue 10 / DOI: 10.52586/4986
Open Access Original Research
Expression of MHC class I polypeptide-related sequence A (MICA) in colorectal cancer
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1 Department of Preventive Medicine, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS 39216, USA
2 Center for Clinical and Translational Science (CCTS), University of Mississippi School of Pharmacy (UMSOP) & University of Mississippi Medical Center, Jackson, MS 39216, USA
3 Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA
4 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
5 Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA
6 CAPES Foundation, Ministry of Education of Brazil, Esplanada dos Ministerios, 70000 Brasilia, Brazil
7 Department of Transplant/Hepatobiliary Surgery, University of Mississippi Medical Center, Jackson, MS 39216, USA
8 O’Neal Comprehensive Cancer Center University of Alabama at Birmingham, Birmingham, AL 35294, USA
9 Division of Hematology, Oncology and Transplantation, Medical School, University of Minnesota, Minneapolis, MN 55455, USA
10 Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
11 Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39216, USA
*Correspondence: christian.gomez@nih.gov (Christian R. Gomez); upendermanne@uabmc.edu (Upender Manne)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2021, 26(10), 765–776; https://doi.org/10.52586/4986
Submitted: 29 July 2021 | Revised: 24 September 2021 | Accepted: 13 October 2021 | Published: 30 October 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Background: The major histocompatibility complex class I polypeptide-related sequence A (MICA) is one of the ligands of the natural killer group 2D (NKG2D) activating receptor. MICA stimulates NKG2D, which further triggers activation of natural killer cells and leads to killing of infected target cells. To subvert the biological function of NKG2D, tumor cells utilize an escape strategy by shedding overexpressed MICA. In this study, we determined the levels of MICA in colorectal cancers (CRCs). Additionally, we established correlations between MICA expression and clinical characteristics. Publicly available data and bioinformatics tools were used for validation purposes. Methods: We determined the MICA RNA expression levels and assessed their correlation with clinicopathological parameters in CRC using the UALCAN web-portal. We performed immunohistochemical analysis on tissue microarrays having 192 samples, acquired from 96 CRC patients, to validate the expression of MICA in CRC and adjacent uninvolved tissue and investigated its prognostic significance by Kaplan-Meier and proportional hazards methods. Results: Bioinformatics and immunohistochemical analyses showed that MICA expression was significantly upregulated in CRCs as compared to uninvolved tissue, and the overexpression of MICA was independent of pathologic stage, histotype, nodal metastasis status, p53-status, as well as patient’s race, age and gender. Moreover, PROGgeneV2 survival analysis of two cohorts showed a poor prognosis for CRC patients exhibiting high MICA expression. Conclusions: Overall, our findings for CRC patients demonstrate generally high expression of MICA, and suggest that a poor prognosis relates to high MICA expression. These results can be further explored due to their potential to provide clues to the contribution of the tumor microenvironment to the progression of CRC.

Keywords
MICA
IHC
Colorectal cancer
Expression
Prognostic marker
Figures
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