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dc.contributor.authorStrauss, Philipp
dc.contributor.authorMarti, Hans-Peter
dc.contributor.authorFurriol, Jessica
dc.contributor.authorNakken, Sigrid
dc.contributor.authorVidar, Beisvåg
dc.contributor.authorEikrem, Øystein Solberg
dc.contributor.authorBeisland, Christian
dc.contributor.authorFlatberg, Arnar
dc.contributor.authorBostad, Leif
dc.contributor.authorScherer, Andreas
dc.contributor.authorEleni, Skandalou
dc.date.accessioned2022-03-18T09:08:07Z
dc.date.available2022-03-18T09:08:07Z
dc.date.created2021-12-11T19:35:51Z
dc.date.issued2021
dc.identifier.issn1475-2867
dc.identifier.urihttps://hdl.handle.net/11250/2986082
dc.description.abstractBackground Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and one of the most common cancers. While survival for localized ccRCC is good, the survival of metastatic disease is not, and thirty percent of patients with ccRCC develop metastases during follow-up. Although current scoring methods accurately identify patients at low progression risk, a small subgroup of those patients still experience metastasis. We therefore aimed to identify ccRCC progression biomarkers in “low-risk” patients who were potentially eligible for adjuvant treatments or more intensive follow-up. Methods We assembled a cohort of ccRCC patients (n  = 443) and identified all “low-risk” patients who later developed progressing tumors (n  = 8). Subsequently, we performed genome-wide expression profiling from formalin-fixed samples obtained at initial surgery from these “low-risk” patients and 16 matched patients not progressing to recurrence with metastasis. The patients were matched for Leibovich sore, creatinine, age, sex, tumor size and tumor stage. Key results were confirmed with qPCR and external data from The Cancer Genome Atlas. Results Principal component analysis indicated that systematic transcriptomic differences were already detectable at the time of initial surgery. One thousand one hundred sixty-seven genes, mainly associated with cancer and immune-related pathways, were differentially expressed between progressors and nonprogressors. A search for a classifier revealed that overexpression of AGAP2-AS1, an antisense long noncoding RNA, correctly classified 23 of 24 samples, years (4.5 years average) in advance of the discovery of metastasis and without requiring larger gene panels. Subsequently, we confirmed AGAP2-AS1 gene overexpression by qPCR in the same samples (p  < 0.05). Additionally, in external data from The Cancer Genome Atlas, overexpression of AGAP2-AS1 is correlated with overall unfavorable survival outcome in ccRCC, irrespective of other prognostic predictors (p  = 2.44E−7). Conclusion AGAP2-AS1 may represent a novel biomarker identifying high-risk ccRCC patients currently classified as “low risk” at the time of surgery.en_US
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleAGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing diseaseen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.source.articlenumber690en_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode1
dc.identifier.doihttps://doi.org/10.1186/s12935-021-02395-9
dc.identifier.cristin1967371
dc.source.journalCancer Cell Internationalen_US
dc.identifier.citationCancer Cell International. 2021, 21, 690en_US
dc.source.volume21en_US


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