Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer
A large body of clinical and experimental evidence indicates that colorectal cancer is one of the most common multifactorial diseases. Although some useful prognostic biomarkers for clinical therapy have already been identified, it is still difficult to characterize a therapeutic signature that is a...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/7/1960 |
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| author | Mariarosaria Conte Annabella Di Mauro Lucia Capasso Liliana Montella Mariacarla De Simone Angela Nebbioso Lucia Altucci |
| author_facet | Mariarosaria Conte Annabella Di Mauro Lucia Capasso Liliana Montella Mariacarla De Simone Angela Nebbioso Lucia Altucci |
| author_sort | Mariarosaria Conte |
| collection | DOAJ |
| description | A large body of clinical and experimental evidence indicates that colorectal cancer is one of the most common multifactorial diseases. Although some useful prognostic biomarkers for clinical therapy have already been identified, it is still difficult to characterize a therapeutic signature that is able to define the most appropriate treatment. Gene expression levels of the epigenetic regulator histone deacetylase 2 (<i>HDAC2</i>) are deregulated in colorectal cancer, and this deregulation is tightly associated with immune dysfunction. By interrogating bioinformatic databases, we identified patients who presented simultaneous alterations in <i>HDAC2</i>, class II major histocompatibility complex transactivator (<i>CIITA)</i>, and beta-2 microglobulin (<i>B2M</i>) genes based on mutation levels, structural variants, and RNA expression levels. We found that <i>B2M</i> plays an important role in these alterations and that mutations in this gene are potentially oncogenic. The dysregulated mRNA expression levels of <i>HDAC2</i> were reported in about 5% of the profiled patients, while other specific alterations were described for <i>CIITA</i>. By analyzing immune infiltrates, we then identified correlations among these three genes in colorectal cancer patients and differential infiltration levels of genetic variants, suggesting that <i>HDAC2</i> may have an indirect immune-related role in specific subgroups of immune infiltrates. Using this approach to carry out extensive immunological signature studies could provide further clinical information that is relevant to more resistant forms of colorectal cancer. |
| first_indexed | 2024-03-11T05:41:39Z |
| format | Article |
| id | doaj.art-2c9f0fd2d364440eb33ce3d20b1c7241 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:41:39Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2c9f0fd2d364440eb33ce3d20b1c72412023-11-17T16:24:07ZengMDPI AGCancers2072-66942023-03-01157196010.3390/cancers15071960Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal CancerMariarosaria Conte0Annabella Di Mauro1Lucia Capasso2Liliana Montella3Mariacarla De Simone4Angela Nebbioso5Lucia Altucci6Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyASL NA2 NORD, Oncology Operative Unit, “Santa Maria delle Grazie” Hospital, 80078 Pozzuoli, ItalyStem Cell Transplantation Unit, Division of Hematology, Cardarelli Hospital, 80131 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyA large body of clinical and experimental evidence indicates that colorectal cancer is one of the most common multifactorial diseases. Although some useful prognostic biomarkers for clinical therapy have already been identified, it is still difficult to characterize a therapeutic signature that is able to define the most appropriate treatment. Gene expression levels of the epigenetic regulator histone deacetylase 2 (<i>HDAC2</i>) are deregulated in colorectal cancer, and this deregulation is tightly associated with immune dysfunction. By interrogating bioinformatic databases, we identified patients who presented simultaneous alterations in <i>HDAC2</i>, class II major histocompatibility complex transactivator (<i>CIITA)</i>, and beta-2 microglobulin (<i>B2M</i>) genes based on mutation levels, structural variants, and RNA expression levels. We found that <i>B2M</i> plays an important role in these alterations and that mutations in this gene are potentially oncogenic. The dysregulated mRNA expression levels of <i>HDAC2</i> were reported in about 5% of the profiled patients, while other specific alterations were described for <i>CIITA</i>. By analyzing immune infiltrates, we then identified correlations among these three genes in colorectal cancer patients and differential infiltration levels of genetic variants, suggesting that <i>HDAC2</i> may have an indirect immune-related role in specific subgroups of immune infiltrates. Using this approach to carry out extensive immunological signature studies could provide further clinical information that is relevant to more resistant forms of colorectal cancer.https://www.mdpi.com/2072-6694/15/7/1960epigeneticscolorectal cancerimmune infiltratespatientmutationgenetic/epigenetic/immunological signature |
| spellingShingle | Mariarosaria Conte Annabella Di Mauro Lucia Capasso Liliana Montella Mariacarla De Simone Angela Nebbioso Lucia Altucci Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer Cancers epigenetics colorectal cancer immune infiltrates patient mutation genetic/epigenetic/immunological signature |
| title | Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer |
| title_full | Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer |
| title_fullStr | Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer |
| title_full_unstemmed | Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer |
| title_short | Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer |
| title_sort | targeting hdac2 mediated immune regulation to overcome therapeutic resistance in mutant colorectal cancer |
| topic | epigenetics colorectal cancer immune infiltrates patient mutation genetic/epigenetic/immunological signature |
| url | https://www.mdpi.com/2072-6694/15/7/1960 |
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