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However, reliable markers for transcriptionally active oncogenes remain elusive due to tumor heterogeneity and confounding signals from non\u2010tumorous cells. We hypothesize that in\u00a0vitro screening is sufficient to identify a long non\u2010coding RNA (lncRNA) signature that is a specific marker for oncogenic transcriptional regulators. Exemplified for the Hippo pathway effectors, we integrated experimental NGS and cancer patient expression data with bioinformatics approaches to identify a yes\u2010associated protein (YAP)\u2010specific lncRNA signature in hepatocellular carcinoma (HCC) cells. The lncRNAs in this signature include CYTOR, MIR4435\u20102HG, SNHG1, and SNHG17, which partly promote HCC cell proliferation and control the sensitivity to YAP\/TEA domain transcription factor (TEAD)\u2010targeted inhibition. In HCC tissues, the lncRNA signature is associated with increased nuclear enrichment of YAP, the expression of YAP target genes, and poor clinical outcomes in patients. This association was also confirmed in cells and tissues of other malignancies, including lung adenocarcinoma (LUAD). Notably, the lncRNA signature is detectable in the serum of HCC patients and predicts YAP activation in tumor tissues.<\/jats:p>\n                  <jats:p>In summary, the Hippo pathway\u2010associated lncRNA signature provides a readout for oncogenic YAP activity across cancers, suggesting its potential as a pan\u2010cancer biomarker. Our results highlight oncogene\u2010specific lncRNA signatures as valuable tools for diagnostics, therapy selection, and treatment monitoring.<\/jats:p>","DOI":"10.1002\/ijc.70584","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:24:14Z","timestamp":1782275054000},"page":"1829-1843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Serum\n                    <scp>lncRNA<\/scp>\n                    Signature Determines Oncogenic\n                    <scp>YAP<\/scp>\n                    Activity in Cancer Patients"],"prefix":"10.1002","volume":"159","author":[{"given":"Fabian","family":"Rose","sequence":"first","affiliation":[{"name":"Institute of Pathology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"El\u2010Ekiaby","sequence":"additional","affiliation":[{"name":"School of Medicine Newgiza 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