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  1. Home
  2. Amplification Of Hippo Signaling Pathway Genes Is Governed And Implicated In The Serous Subtype-specific Ovarian Carcino-genesis.
  1. Home
  2. Amplification Of Hippo Signaling Pathway Genes Is Governed And Implicated In The Serous Subtype-specific Ovarian Carcino-genesis.

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Amplification of Hippo Signaling Pathway Genes Is Governed and Implicated in the Serous Subtype-Specific Ovarian

Karthik Balakrishnan1, Yuanhong Chen1, Jixin Dong1

  • 1Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Cancers
|May 11, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

The Hippo signaling pathway is significantly dysregulated in serous ovarian cancer, with specific genes like YAP1 and MST1 acting as potential biomarkers for early detection and targeted therapies.

Keywords:
Hippo signaling pathwayamplificationovarian cancerserous subtype

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer is a leading cause of cancer death in women.
  • The Hippo signaling pathway's role in ovarian carcinogenesis is not fully understood.
  • Identifying key molecular pathways is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the impact of the Hippo signaling pathway on ovarian carcinogenesis.
  • To identify specific Hippo signaling pathway signatures associated with ovarian cancer subtypes.
  • To evaluate the potential of these signatures as biomarkers for serous ovarian cancer.

Main Methods:

  • Utilized the Molecular Signatures Database (MSigDB) for Hippo signaling pathway signatures.
  • Employed Z score-based pathway activation scoring on mRNA expression profiles.
  • Performed Receiver Operating Characteristic (ROC) curve analysis for gene set prediction.
  • Conducted mutation analysis using the cBioPortal database.
  • Analyzed Dependency Map (DepMap) data for gene amplification in cell lines.
  • Investigated overall survival (OS) curves.
  • Main Results:

    • Hippo signaling pathway signatures are prominently dysregulated in serous ovarian cancer subtypes.
    • YAP1 and MST1 gene sets demonstrated high specificity and sensitivity in predicting serous tumors.
    • Hippo signaling pathway genes show high amplification in advanced-stage (grade 3, stage 3/4) high-grade serous ovarian adenocarcinoma.
    • Significant amplification of these genes was observed across ovarian cancer cell lines.
    • High expression of these genes correlates with poor overall survival in serous ovarian cancer patients (p < 0.05).

    Conclusions:

    • The Hippo signaling pathway plays a significant role in serous ovarian carcinogenesis.
    • YAP1 and MST1 are potential predictive biomarkers for serous ovarian cancer.
    • Findings support the development of targeted therapies for serous ovarian cancer based on Hippo pathway dysregulation.