High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein–Barr Virus-Associated Gastric Adenocarcinomas
<p>Expression of classical MHC-I heavy chain gene mRNA in gastric carcinoma subtypes and normal gastric tissue. RNA-Sequencing by Expectation Maximization (RSEM) normalized data for the HLA-A (<b>A</b>), HLA-B (<b>B</b>) and HLA-C (<b>C</b>) MHC-I heavy chain genes were extracted from The Cancer Genome Atlas (TCGA) database for the TCGA/PanCancer Atlas gastric/stomach adenocarcinoma (STAD) cohort for EBV-associated gastric carcinomas (EBVaGCs), normal control tissues, and three other gastric cancer (GC) subtypes. False discovery rate (FDR)-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel. CIN: chromosomal instability; GS: genomically stable; MSI: microsatellite instability.</p> "> Figure 2
<p>Expression of non-classical MHC-I heavy chain genes and light chain in gastric carcinoma subtypes and normal gastric tissue. Normalized RNA-seq data for the HLA-E (<b>A</b>), HLA-F (<b>B</b>) and HLA-G (<b>C</b>) MHC-I heavy chain and B2M (<b>D</b>) light chain genes were extracted from the TCGA database for the STAD cohort for EBVaGCs, normal control tissues, and three other GC subtypes. FDR-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel.</p> "> Figure 3
<p>Expression levels of the TAP genes involved in MHC-I-dependent antigen presentation in gastric carcinoma subtypes and normal gastric tissue. Normalized RNA-seq data for the TAP1 (<b>A</b>), TAP2 (<b>B</b>) and TAPBP (<b>C</b>) genes involved in MHC-I-dependent antigen presentation were extracted from the TCGA database for the STAD cohort for EBVaGCs, normal control tissues, and three other GC subtypes. FDR-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel.</p> "> Figure 4
<p>Expression levels of other genes involved in MHC-I-dependent antigen loading in gastric carcinoma subtypes and normal gastric tissue. Normalized RNA-seq data for the CANX (<b>A</b>), CALR (<b>B</b>), PDIA3 (<b>C</b>), ERAP1 (<b>D</b>) and ERAP2 (<b>E</b>) genes involved in MHC-I-dependent antigen presentation were extracted from the TCGA database for the STAD cohort for EBVaGCs, normal control tissues, and three other GC subtypes. FDR-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel.</p> "> Figure 5
<p>Detection of tumor infiltrating T cells and natural killer (NK) cells in gastric carcinoma subtypes and normal gastric tissue. Normalized RNA-seq data for genes indicative of tumor infiltrating T cells including CD3D (<b>A</b>), CD3E (<b>B</b>), and CD3G (<b>C</b>), or FCGR3A (<b>D</b>) for NK cells were extracted from the TCGA database for the STAD cohort for EBVaGCs, normal control tissues, and three other GC subtypes. FDR-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel.</p> "> Figure 6
<p>Expression of mRNA encoding IFN-γ and transcription factors involved in regulating the interferon-dependent activation of MHC-I-dependent antigen presentation and loading genes. Normalized RNA-seq data for the IFN-γ (IFNG) gene (<b>A</b>) and the genes encoding the nucleotide-binding oligomerization domain (NOD)-like receptor caspase recruitment domain containing protein 5 (NLRC5)/MHC-I transactivator (CITA; panel (<b>B</b>)) and Regulatory Factor X5 (RFX5; panel (<b>C</b>)) transcription factors involved in interferon-induced activation of expression of genes involved in MHC-I-dependent antigen presentation were extracted from the TCGA database for the STAD cohort for EBVaGCs, normal control tissues, and three other GC subtypes. FDR-adjusted <span class="html-italic">p</span>-values for each statistical comparison are shown on the right for each gene panel.</p> "> Figure 7
<p>Correlation matrix of selected genes involved in the MHC-I antigen presentation pathway. Heatmap of Spearman correlation analysis of mRNA expression of the indicated MHC-I pathway genes in EBVaGC (<b>A</b>). Comparisons with EBV genes reported to antagonize interferon-γ response are also shown. For comparison, Spearman correlations between mRNA levels for interferon-γ (IFNG) and MHC-I pathway genes are also shown for the CIN (<b>B</b>), GS (<b>C</b>), and MSI (<b>D</b>) subtypes. RSEM normalized RNA-seq data for the genes listed above were extracted from the TCGA database for the STAD cohort for EBVaGCs. Pairwise spearman correlations were performed. Numbers in boxes indicate Spearman’s rank correlation coefficient of analyzed gene pairs and <span class="html-italic">p</span>-values.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. RNA Expression Comparisons and Statistical Analysis
2.2. Correlation Matrix
3. Results
3.1. Correlation between mRNA Expression Levels of MHC-I Genes, EBV Status, and Clinical Variables in Human Gastric Cancers
3.2. Impact of EBV Status on MHC-I Heavy Chain mRNA Expression in Human Gastric Cancers
3.3. Impact of EBV Status on the Expression of mRNA Encoding Other Components of the MHC-I Antigen Presentation Apparatus in Human Gastric Cancers
3.4. Higher Levels of Lymphocytes, and Interferon γ are Present in EBV-Associated Gastric Carcinomas
3.5. Impact of EBV Status on mRNA Levels of the Transcriptional Regulators of MHC-I Gene Expression
4. Discussion
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Variables | |||||
---|---|---|---|---|---|---|
EBV Status | Sex | Age | ||||
Negative | Positive | Female | Male | Median (Max-Min) | ||
HLA-A | High | 164 | 24 | 63 | 128 | 68 (90–41) |
Low | 186 | 6 | 68 | 124 | 66 (90–30) | |
p-value | 1.16 × 10−3 | 6.94 × 10−1 | 8.35 × 10−2 | |||
HLA-B | High | 166 | 25 | 65 | 126 | 67 (90–35) |
Low | 187 | 5 | 66 | 126 | 67 (90–35) | |
p-value | 2.85 × 10−4 | 1.00 | 6.71 × 10−1 | |||
HLA-C | High | 165 | 26 | 66 | 125 | 68 (90–39) |
Low | 188 | 4 | 65 | 127 | 66 (87–30) | |
p-value | 6.11 × 10−5 | 9.71 × 10−1 | 2.42 × 10−1 | |||
B2M | High | 165 | 26 | 69 | 122 | 68 (90–39) |
Low | 188 | 4 | 62 | 130 | 67 (90–30) | |
p-value | 6.11 × 10−5 | 4.95 × 10−1 | 7.52 × 10−1 | |||
TAP1 | High | 162 | 29 | 62 | 129 | 68 (90–35) |
Low | 191 | 1 | 69 | 123 | 67 (90–30) | |
p-value | 2.61 × 10−7 | 5.42 × 10−1 | 2.20 × 10−1 | |||
TAP2 | High | 165 | 26 | 61 | 130 | 68 (90–39) |
Low | 188 | 4 | 70 | 122 | 67 (90–30) | |
p-value | 6.11 × 10−5 | 4.50 × 10−1 | 4.69 × 10−1 | |||
TAPBP | High | 169 | 22 | 64 | 127 | 68 (90–30) |
Low | 184 | 8 | 67 | 125 | 67 (90–34) | |
p-value | 1.29 × 10−2 | 8.58 × 10−1 | 2.40 × 10−1 |
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Ghasemi, F.; Gameiro, S.F.; Tessier, T.M.; Maciver, A.H.; Mymryk, J.S. High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein–Barr Virus-Associated Gastric Adenocarcinomas. Cells 2020, 9, 499. https://doi.org/10.3390/cells9020499
Ghasemi F, Gameiro SF, Tessier TM, Maciver AH, Mymryk JS. High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein–Barr Virus-Associated Gastric Adenocarcinomas. Cells. 2020; 9(2):499. https://doi.org/10.3390/cells9020499
Chicago/Turabian StyleGhasemi, Farhad, Steven F. Gameiro, Tanner M. Tessier, Allison H. Maciver, and Joe S. Mymryk. 2020. "High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein–Barr Virus-Associated Gastric Adenocarcinomas" Cells 9, no. 2: 499. https://doi.org/10.3390/cells9020499