Expression of MHC class I polypeptide-related sequence A (MICA) in colorectal cancer

Ingrid Espinoza, Sumit Agarwal, Marcelo Sakiyama, Veena Shenoy, Wayne S. Orr, Sameer Al Diffalha, Anna Prizment, Sooryanarayana Varambally, Upender Manne, Christian R. Gomez

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)765-776
Number of pages12
JournalFrontiers in Bioscience - Landmark
Volume26
Issue number10
DOIs
StatePublished - Oct 30 2021

Bibliographical note

Funding Information:
This study was supported by the Office of Research and Sponsored Programs, University of Mississippi Medical Center (IE and CRG); Coordination for the Improvement of the Higher Education Personnel (CAPES) Foundation, Scholarship #13603-13-2 (MJS), and the Impact Funds from the School of Medicine and the Department of Pathology, University of Alabama at Birmingham (UM).

Publisher Copyright:
© 2021 Frontiers in Bioscience. All rights reserved.

Keywords

  • Colorectal cancer
  • Expression
  • IHC
  • MICA
  • Prognostic marker

Fingerprint

Dive into the research topics of 'Expression of MHC class I polypeptide-related sequence A (MICA) in colorectal cancer'. Together they form a unique fingerprint.

Cite this