Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains
The IgLON family of tumor suppressor genes (TSG) impact a variety of cellular processes involved in cancer and non-cancer biology. OPCML is a member of this family and its inactivation is an important control point in oncogenesis and tumor growth. Here, we analyze RNA-Seq expression ratios in ovaria...
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2025-05-01
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| author | Adam G. Marsh Franziska Görtler Sassan Hafizi Hani Gabra |
| author_facet | Adam G. Marsh Franziska Görtler Sassan Hafizi Hani Gabra |
| author_sort | Adam G. Marsh |
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| description | The IgLON family of tumor suppressor genes (TSG) impact a variety of cellular processes involved in cancer and non-cancer biology. OPCML is a member of this family and its inactivation is an important control point in oncogenesis and tumor growth. Here, we analyze RNA-Seq expression ratios in ovarian cancers from The Cancer Genome Atlas (TCGA) (189 subjects at Stage III) to identify genes that exhibit a cooperative survival impact (via Kaplan–Meier survival curves) with OPCML expression. Using enrichment analyses, we reconstruct functional pathway impacts revealing interactions of OPCML, and then validate these in independent cohorts of ovarian cancer. These results emphasize the role of OPCML’s regulation of receptor tyrosine kinase (RTK) signaling pathways (PI3K/AKT and MEK/ERK) while identifying three new potential RTK transcriptomic linkages to KIT, TEK, and ROS1 in ovarian cancer. We show that other known extracellular signaling receptor ligands are also transcriptionally linked to OPCML. Several key genes were validated in GEO datasets, including KIT and TEK. Considering the range of OPCML impacts evident in our analyses on both external membrane interactions and cytosolic signal transduction, we expand the understanding of OPCML’s broad cellular influences, demonstrating a multi-functional, pleiotropic, tumor suppressor, in keeping with prior published studies of OPCML function. |
| format | Article |
| id | doaj-art-2fb4ced7773b483f9add98c1f9e0ef80 |
| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-2fb4ced7773b483f9add98c1f9e0ef802025-08-20T03:27:10ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147640510.3390/cimb47060405Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig DomainsAdam G. Marsh0Franziska Görtler1Sassan Hafizi2Hani Gabra3Center for Computational Biology and Bioinformatics, University of Delaware, Newark, DE 19716, USADepartment of Oncology and Medical Physics, Haukeland University Hospital, 5009 Bergen, NorwaySchool of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UKPapyrus Therapeutics Inc., Philadelphia, PA 19104, USAThe IgLON family of tumor suppressor genes (TSG) impact a variety of cellular processes involved in cancer and non-cancer biology. OPCML is a member of this family and its inactivation is an important control point in oncogenesis and tumor growth. Here, we analyze RNA-Seq expression ratios in ovarian cancers from The Cancer Genome Atlas (TCGA) (189 subjects at Stage III) to identify genes that exhibit a cooperative survival impact (via Kaplan–Meier survival curves) with OPCML expression. Using enrichment analyses, we reconstruct functional pathway impacts revealing interactions of OPCML, and then validate these in independent cohorts of ovarian cancer. These results emphasize the role of OPCML’s regulation of receptor tyrosine kinase (RTK) signaling pathways (PI3K/AKT and MEK/ERK) while identifying three new potential RTK transcriptomic linkages to KIT, TEK, and ROS1 in ovarian cancer. We show that other known extracellular signaling receptor ligands are also transcriptionally linked to OPCML. Several key genes were validated in GEO datasets, including KIT and TEK. Considering the range of OPCML impacts evident in our analyses on both external membrane interactions and cytosolic signal transduction, we expand the understanding of OPCML’s broad cellular influences, demonstrating a multi-functional, pleiotropic, tumor suppressor, in keeping with prior published studies of OPCML function.https://www.mdpi.com/1467-3045/47/6/405OPCMLovarian cancerIgLON gene familytumor suppressor genesRTK suppression |
| spellingShingle | Adam G. Marsh Franziska Görtler Sassan Hafizi Hani Gabra Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains Current Issues in Molecular Biology OPCML ovarian cancer IgLON gene family tumor suppressor genes RTK suppression |
| title | Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains |
| title_full | Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains |
| title_fullStr | Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains |
| title_full_unstemmed | Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains |
| title_short | Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains |
| title_sort | bioinformatic rna seq functional profiling of the tumor suppressor gene opcml in ovarian cancers the multifunctional pleiotropic impacts of having three ig domains |
| topic | OPCML ovarian cancer IgLON gene family tumor suppressor genes RTK suppression |
| url | https://www.mdpi.com/1467-3045/47/6/405 |
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