CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy
<i>Background and Objectives</i>: 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...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/2/190 |
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| author | Carol K. Balakrishnan Gee Jun Tye Shandra Devi Balasubramaniam Gurjeet Kaur |
| author_facet | Carol K. Balakrishnan Gee Jun Tye Shandra Devi Balasubramaniam Gurjeet Kaur |
| author_sort | Carol K. Balakrishnan |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: 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). <i>Materials and Methods</i>: 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. <i>Results</i>: 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 (<i>p</i> = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (<i>p</i> = 0.001 and <i>p</i> = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-09T21:29:46Z |
| format | Article |
| id | doaj.art-a46e360ec5294b5a8c5a004d349b2159 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T21:29:46Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-a46e360ec5294b5a8c5a004d349b21592023-11-23T20:59:25ZengMDPI AGMedicina1010-660X1648-91442022-01-0158219010.3390/medicina58020190CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour TherapyCarol K. Balakrishnan0Gee Jun Tye1Shandra Devi Balasubramaniam2Gurjeet Kaur3Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia<i>Background and Objectives</i>: 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). <i>Materials and Methods</i>: 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. <i>Results</i>: 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 (<i>p</i> = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (<i>p</i> = 0.001 and <i>p</i> = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/58/2/190CD74HLA-DRAcervical cancercervical intraepithelial neoplasia |
| spellingShingle | Carol K. Balakrishnan Gee Jun Tye Shandra Devi Balasubramaniam Gurjeet Kaur CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy Medicina CD74 HLA-DRA cervical cancer cervical intraepithelial neoplasia |
| 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 | CD74 HLA-DRA cervical cancer cervical intraepithelial neoplasia |
| url | https://www.mdpi.com/1648-9144/58/2/190 |
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