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

Ingrid Espinoza ,Sooryanarayana Varambally ,Sameer Al Diffalha ,Marcelo J Sakiyama ,Upender Manne ,Veena Shenoy ,Sumit Agarwal ,Anna E Prizment ,W Shannon Orr ,Christian R Gómez

doi:10.52586/4986

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.

Highlights

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 transcripts were elevated regardless of race in colon and rectum (CRC), when tumors of Caucasian (N = 193), p < 0.0001; African-American (N = 55), p = 0.002; and Asian (N = 11), p = 0.022 CRC patients were compared to uninvolved tissue (Fig. 1D)
Further analysis showed that MICA RNA expression based on histological subtypes was higher in CRCs than in uninvolved tissues (Fig. 1F)

Summary

Introduction

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. 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. Upon interaction with natural killer group 2D (NKG2D) receptors, MICA promotes activation of natural killer (NK) cells, IFN-gamma secretion, and degranulation of perforin and granzymes, leading to apoptosis of cells expressing high levels of MICA [3, 4]. MICA has been proposed as a relevant player of the tumor microenvironment (TME) [7], worth to be explored as a factor of tumorigenesis

Methods

Results

Discussion

Conclusion