Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer
Abstract Background ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting mach...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-10785-7 |
| _version_ | 1797836403580600320 |
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| author | Marta Wagner Maciej Sobczyński Monika Jasek Konrad Pawełczyk Irena Porębska Piotr Kuśnierczyk Andrzej Wiśniewski |
| author_facet | Marta Wagner Maciej Sobczyński Monika Jasek Konrad Pawełczyk Irena Porębska Piotr Kuśnierczyk Andrzej Wiśniewski |
| author_sort | Marta Wagner |
| collection | DOAJ |
| description | Abstract Background ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting machinery – APM, ERAP1 is frequently down-regulated in many cancers. Since ERAP1 expression has not yet been thoroughly investigated in non-small cell lung cancer (NSCLC), we decided to analyze ERAP1 mRNA levels in tissues collected from NSCLC patients. Methods Using real-time qPCR, we evaluated ERAP1 mRNA expression in samples of tumor and adjacent non-tumor tissue (serving as control tissue) from 61 NSCLC patients. Results We observed a significantly lower level of ERAP1 mRNA expression in tumor tissue (MedTumor = 0.75) in comparison to non-tumor tissue (MedNon-tumor = 1.1), p = 0.008. One of the five tested polymorphisms, namely rs26653, turned out to be significantly associated with ERAP1 expression in non-tumor tissue (difference [d] = 0.59 CI95% (0.14;1.05), p = 0.0086), but not in tumor tissue. The levels of ERAP1 mRNA expression did not affect the overall survival of NSCLC patients, either in the case of the tumor (p = 0.788) or in non-tumor (p = 0.298) tissue. We did not detect any association between mRNA ERAP1 expression level in normal tissue and: (i) age at diagnosis (p = 0.8386), (ii) patient’s sex (p = 0.3616), (iii) histological type of cancer (p = 0.7580) and (iv) clinical stage of NSCLC (p = 0.7549). Furthermore, in the case of tumor tissue none of the abovementioned clinical parameters were associated with ERAP1 expression (p = 0.76). Conclusion Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy. The rs26653 polymorphism can be considered an expression quantitative trait locus (eQTL) associated with ERAP1 expression in normal lung tissue. |
| first_indexed | 2024-04-09T15:08:17Z |
| format | Article |
| id | doaj.art-2fd09f652c504e798f11234d08673fab |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T15:08:17Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-2fd09f652c504e798f11234d08673fab2023-04-30T11:18:47ZengBMCBMC Cancer1471-24072023-04-0123111110.1186/s12885-023-10785-7Down-regulation of ERAP1 mRNA expression in non-small cell lung cancerMarta Wagner0Maciej Sobczyński1Monika Jasek2Konrad Pawełczyk3Irena Porębska4Piotr Kuśnierczyk5Andrzej Wiśniewski6Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of SciencesLaboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesDepartment of Thoracic Surgery, Lower Silesian Centre of Oncology, Pulmonology and HaematologyDepartment of Pulmonology and Lung Oncology, Wrocław Medical UniversityLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesAbstract Background ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting machinery – APM, ERAP1 is frequently down-regulated in many cancers. Since ERAP1 expression has not yet been thoroughly investigated in non-small cell lung cancer (NSCLC), we decided to analyze ERAP1 mRNA levels in tissues collected from NSCLC patients. Methods Using real-time qPCR, we evaluated ERAP1 mRNA expression in samples of tumor and adjacent non-tumor tissue (serving as control tissue) from 61 NSCLC patients. Results We observed a significantly lower level of ERAP1 mRNA expression in tumor tissue (MedTumor = 0.75) in comparison to non-tumor tissue (MedNon-tumor = 1.1), p = 0.008. One of the five tested polymorphisms, namely rs26653, turned out to be significantly associated with ERAP1 expression in non-tumor tissue (difference [d] = 0.59 CI95% (0.14;1.05), p = 0.0086), but not in tumor tissue. The levels of ERAP1 mRNA expression did not affect the overall survival of NSCLC patients, either in the case of the tumor (p = 0.788) or in non-tumor (p = 0.298) tissue. We did not detect any association between mRNA ERAP1 expression level in normal tissue and: (i) age at diagnosis (p = 0.8386), (ii) patient’s sex (p = 0.3616), (iii) histological type of cancer (p = 0.7580) and (iv) clinical stage of NSCLC (p = 0.7549). Furthermore, in the case of tumor tissue none of the abovementioned clinical parameters were associated with ERAP1 expression (p = 0.76). Conclusion Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy. The rs26653 polymorphism can be considered an expression quantitative trait locus (eQTL) associated with ERAP1 expression in normal lung tissue.https://doi.org/10.1186/s12885-023-10785-7Non-small cell lung cancerERAP1 mRNA expressionrs26653eQTLGenetics |
| spellingShingle | Marta Wagner Maciej Sobczyński Monika Jasek Konrad Pawełczyk Irena Porębska Piotr Kuśnierczyk Andrzej Wiśniewski Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer BMC Cancer Non-small cell lung cancer ERAP1 mRNA expression rs26653 eQTL Genetics |
| title | Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer |
| title_full | Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer |
| title_fullStr | Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer |
| title_full_unstemmed | Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer |
| title_short | Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer |
| title_sort | down regulation of erap1 mrna expression in non small cell lung cancer |
| topic | Non-small cell lung cancer ERAP1 mRNA expression rs26653 eQTL Genetics |
| url | https://doi.org/10.1186/s12885-023-10785-7 |
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