Related Experiment Video
Updated: Sep 14, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The
Adam G Marsh1, Franziska Görtler2, Sassan Hafizi3
1Center for Computational Biology and Bioinformatics, University of Delaware, Newark, DE 19716, USA.
Abstract:
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.
Insights
The tumor suppressor gene OPCML plays a crucial role in ovarian cancer. Its regulation impacts key signaling pathways, offering new therapeutic targets for this disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The IgLON family of tumor suppressor genes (TSG) influences cancer and non-cancer cellular processes.
- OPCML gene inactivation is a critical factor in oncogenesis and tumor progression.
Purpose of the Study:
- To identify genes that cooperate with OPCML expression to impact survival in Stage III ovarian cancer.
- To elucidate the functional pathways and interactions associated with OPCML in ovarian cancer.
Main Methods:
- Analysis of RNA-Seq expression data from The Cancer Genome Atlas (TCGA) for 189 Stage III ovarian cancer patients.
- Kaplan-Meier survival analysis to assess the cooperative survival impact of gene expression.
- Enrichment analyses to reconstruct functional pathways and identify gene interactions.
- Validation of findings in independent ovarian cancer cohorts and GEO datasets.
Main Results:
- OPCML expression is linked to survival in ovarian cancer.
- OPCML regulates receptor tyrosine kinase (RTK) signaling pathways, including PI3K/AKT and MEK/ERK.
- Identified novel RTK transcriptomic linkages with KIT, TEK, and ROS1 in ovarian cancer.
- Other extracellular signaling receptor ligands were found to be transcriptionally linked to OPCML.
- Validation of KIT and TEK linkages in independent datasets.
Conclusions:
- OPCML functions as a pleiotropic tumor suppressor in ovarian cancer.
- OPCML's regulation of RTK signaling pathways is crucial for its tumor suppressor activity.
- The study expands the understanding of OPCML's cellular influence, highlighting its role in both external membrane interactions and cytosolic signal transduction.
More Related Videos
Related Concept Videos
02:24Ribosome Profiling
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
03:21RNA-seq
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...