A Serum lncRNA Signature Determines Oncogenic YAP Activity in Cancer Patients

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Identifying biomarkers for active oncogenes is challenging due to tumor heterogeneity.
• Reliable markers for transcriptionally active oncogenes are needed for cancer diagnostics and therapy.

Purpose of the Study:

• To identify a long non-coding RNA (lncRNA) signature specific to oncogenic transcriptional regulators, exemplified by the Hippo pathway.
• To validate this signature as a potential pan-cancer biomarker detectable in patient serum.

Main Methods:

• Integrated Next-Generation Sequencing (NGS) and cancer patient expression data.
• Employed bioinformatics to identify a Yes-associated protein (YAP)-specific lncRNA signature in hepatocellular carcinoma (HCC).
• Validated findings in HCC tissues, other malignancies (LUAD), and patient serum.

Main Results:

• Identified a YAP-specific lncRNA signature (CYTOR, MIR4435-2HG, SNHG1, SNHG17) promoting HCC proliferation.
• The signature correlates with YAP activity, target gene expression, and poor outcomes in HCC and LUAD.
• The lncRNA signature in serum predicts YAP activation and clinical outcomes.

Conclusions:

• The Hippo pathway-associated lncRNA signature serves as a readout for oncogenic YAP activity across cancers.
• This signature demonstrates potential as a pan-cancer biomarker for diagnostics, therapy selection, and monitoring.
• Oncogene-specific lncRNA signatures are valuable tools in cancer research and clinical applications.