Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achievi...
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5301 |
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| author | Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo |
| author_facet | Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo |
| author_sort | Robert A. Szczepaniak Sloane |
| collection | DOAJ |
| description | Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors. |
| first_indexed | 2024-03-10T06:05:54Z |
| format | Article |
| id | doaj.art-c8064d6d4da44883816ebcc8ea0a1965 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:05:54Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c8064d6d4da44883816ebcc8ea0a19652023-11-22T20:33:13ZengMDPI AGCancers2072-66942021-10-011321530110.3390/cancers13215301Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade OutcomesRobert A. Szczepaniak Sloane0Michael G. White1Russell G. Witt2Anik Banerjee3Michael A. Davies4Guangchun Han5Elizabeth Burton6Nadim Ajami7Julie M. Simon8Chantale Bernatchez9Lauren E. Haydu10Hussein A. Tawbi11Jeffrey E. Gershenwald12Emily Keung13Merrick Ross14Jennifer McQuade15Rodabe N. Amaria16Khalida Wani17Alexander J. Lazar18Scott E. Woodman19Linghua Wang20Miles C. Andrews21Jennifer A. Wargo22Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Biologics Development, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAMetastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors.https://www.mdpi.com/2072-6694/13/21/5301microRNAmelanomaimmune checkpoint blockade |
| spellingShingle | Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes Cancers microRNA melanoma immune checkpoint blockade |
| title | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
| title_full | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
| title_fullStr | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
| title_full_unstemmed | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
| title_short | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
| title_sort | identification of microrna mrna networks in melanoma and their association with pd 1 checkpoint blockade outcomes |
| topic | microRNA melanoma immune checkpoint blockade |
| url | https://www.mdpi.com/2072-6694/13/21/5301 |
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