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CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy
Background and Objectives: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression fro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877221/ https://www.ncbi.nlm.nih.gov/pubmed/35208514 http://dx.doi.org/10.3390/medicina58020190 |
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author | Balakrishnan, Carol K. Tye, Gee Jun Balasubramaniam, Shandra Devi Kaur, Gurjeet |
author_facet | Balakrishnan, Carol K. Tye, Gee Jun Balasubramaniam, Shandra Devi Kaur, Gurjeet |
author_sort | Balakrishnan, Carol K. |
collection | PubMed |
description | Background and Objectives: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression from normal cervix to precancerous cervical intraepithelial neoplasia (CIN) and finally to squamous cell carcinoma (SCC). Materials and Methods: The gene expression profiles of CD74 and HLA-DRA were determined in formalin-fixed paraffin-embedded tissues, with three samples each from normal cervixes, human papillomavirus type 16/18-positive, low-grade CIN (LGCIN), high-grade CIN (HGCIN), and squamous cell carcinoma (SCC) using Human Transcriptome Array 2.0. Immunohistochemical expression of the proteins was semi-quantitatively assessed in another cohort of tissue microarray samples comprising 7 normal cervix cases, 10 LGCIN, 10 HGCIN, and 95 SCC. Results: The transcriptomics profile and proteins’ expression demonstrated similar trends of upregulation of CD74 and HLA-DRA from normal cervix to CIN and highest in SCC. There was a significant difference in both proteins’ expression between the histological groups (p = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (p = 0.001 and p = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. Conclusions: CD74 appears to promote cervical carcinogenesis via oncogenic signalling mechanisms and may serve as a potential antitumour target. Additionally, the upregulation of HLA-DRA, often associated with stronger immunogenicity, could be a promising biomarker for developing immunotherapies. |
format | Online Article Text |
id | pubmed-8877221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88772212022-02-26 CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy Balakrishnan, Carol K. Tye, Gee Jun Balasubramaniam, Shandra Devi Kaur, Gurjeet Medicina (Kaunas) Article Background and Objectives: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression from normal cervix to precancerous cervical intraepithelial neoplasia (CIN) and finally to squamous cell carcinoma (SCC). Materials and Methods: The gene expression profiles of CD74 and HLA-DRA were determined in formalin-fixed paraffin-embedded tissues, with three samples each from normal cervixes, human papillomavirus type 16/18-positive, low-grade CIN (LGCIN), high-grade CIN (HGCIN), and squamous cell carcinoma (SCC) using Human Transcriptome Array 2.0. Immunohistochemical expression of the proteins was semi-quantitatively assessed in another cohort of tissue microarray samples comprising 7 normal cervix cases, 10 LGCIN, 10 HGCIN, and 95 SCC. Results: The transcriptomics profile and proteins’ expression demonstrated similar trends of upregulation of CD74 and HLA-DRA from normal cervix to CIN and highest in SCC. There was a significant difference in both proteins’ expression between the histological groups (p = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (p = 0.001 and p = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. Conclusions: CD74 appears to promote cervical carcinogenesis via oncogenic signalling mechanisms and may serve as a potential antitumour target. Additionally, the upregulation of HLA-DRA, often associated with stronger immunogenicity, could be a promising biomarker for developing immunotherapies. MDPI 2022-01-26 /pmc/articles/PMC8877221/ /pubmed/35208514 http://dx.doi.org/10.3390/medicina58020190 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Balakrishnan, Carol K. Tye, Gee Jun Balasubramaniam, Shandra Devi Kaur, Gurjeet CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title | CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title_full | CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title_fullStr | CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title_full_unstemmed | CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title_short | CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy |
title_sort | cd74 and hla-dra in cervical carcinogenesis: potential targets for antitumour therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877221/ https://www.ncbi.nlm.nih.gov/pubmed/35208514 http://dx.doi.org/10.3390/medicina58020190 |
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