Dataset Information

Expression of human leukocyte antigen class I and ?2-microglobulin in colorectal cancer and its prognostic impact.

ABSTRACT: Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability-high (MSI-H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and ?2-microglobulin (?2M) expression in MSI-H and microsatellite-stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI-H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, ?2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI-H and 54 (38.8%) MSS cases, while reduced ?2M expression was observed in 69 (42.9%) MSI-H and 17 (12.2%) MSS cases. Although reduced ?2M expression was associated with higher pathological tumor (pT) stage in MSI-H CRC with borderline significance, no association was found between HLA A/B/C and ?2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and ?2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and ?2M expression was frequently observed in immunotherapy-naive MSI-H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and ?2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and ?2M might be a feasible predictive or prognostic tool in CRC.

SUBMITTER: Na HY

PROVIDER: S-EPMC7780028 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Expression of human leukocyte antigen class I and β2-microglobulin in colorectal cancer and its prognostic impact.

Na Hee Young HY Park Yujun Y Nam Soo Kyung SK Lee Kyu Sang KS Oh Heung-Kwon HK Kim Duck-Woo DW Kang Sung-Bum SB Kim Woo Ho WH Lee Hye Seung HS

Cancer science 20201128 1

Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability-high (MSI-H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2-microglobulin (β2M) expression in MSI-H and microsatellite-stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI-H a ...[more]

PMID: 33159376

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Project description:Class II human leukocyte antigens (HLA II) are proteins involved in the human immunological adaptive response by binding and exposing some pre-processed, non-self peptides in the extracellular domain in order to make them recognizable by the CD4+ T lymphocytes. However, the understanding of HLA-peptide binding interaction is a crucial step for designing a peptide-based vaccine because the high rate of polymorphisms in HLA class II molecules creates a big challenge, even though the HLA II proteins can be grouped into supertypes, where members of different class bind a similar pool of peptides. Hence, first we performed the supertype classification of 27 HLA II proteins using their binding affinities and structural-based linear motifs to create a stable group of supertypes. For this purpose, a well-known clustering method was used, and then, a consensus was built to find the stable groups and to show the functional and structural correlation of HLA II proteins. Thus, the overlap of the binding events was measured, confirming a large promiscuity within the HLA II-peptide interactions. Moreover, a very low rate of locus-specific binding events was observed for the HLA-DP genetic locus, suggesting a different binding selectivity of these proteins with respect to HLA-DR and HLA-DQ proteins. Secondly, a predictor based on a support vector machine (SVM) classifier was designed to recognize HLA II-binding peptides. The efficiency of prediction was estimated using precision, recall (sensitivity), specificity, accuracy, F-measure, and area under the ROC curve values of random subsampled dataset in comparison with other supervised classifiers. Also the leave-one-out cross-validation was performed to establish the efficiency of the predictor. The availability of HLA II-peptide interaction dataset, HLA II-binding motifs, high-quality amino acid indices, peptide dataset for SVM training, and MATLAB code of the predictor is available at http://sysbio.icm.edu.pl/HLA .

Dataset Information

Expression of human leukocyte antigen class I and ?2-microglobulin in colorectal cancer and its prognostic impact.

Publications

Expression of human leukocyte antigen class I and β2-microglobulin in colorectal cancer and its prognostic impact.

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