{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:44:22Z","timestamp":1791233062572,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Plasma\u2010derived tumour\u2010specific cell\u2010free nucleic acids are increasingly utilized as a minimally invasive, real\u2010time biomarker approach in many solid tumours. Circulating tumour DNA of melanoma\u2010specific mutations is currently the best studied liquid biopsy biomarker for melanoma. However, the combination of hotspot genetic alterations covers only around 80% of all melanoma patients. Therefore, alternative approaches are needed to enable the follow\u2010up of all genotypes, including wild\u2010type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>KPNA2<\/jats:italic>\n                      ,\n                      <jats:italic>DTL<\/jats:italic>\n                      ,\n                      <jats:italic>BACE2<\/jats:italic>\n                      and\n                      <jats:italic>DTYMK<\/jats:italic>\n                      messenger RNA (mRNA) upregulated in melanoma versus nevi tissues by unsupervised data mining (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0175 melanoma,\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a020 normal skin,\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a06 benign nevi) and experimentally confirmed differential mRNA expression in vitro (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a018 melanoma,\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a08 benign nevi). Circulating cell\u2010free RNA (cfRNA) was analysed in 361 plasma samples (collected before and during therapy) from 100 melanoma patients and 18 healthy donors. Absolute cfRNA copies were quantified on droplet digital PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>KPNA2<\/jats:italic>\n                      ,\n                      <jats:italic>DTL<\/jats:italic>\n                      ,\n                      <jats:italic>BACE2<\/jats:italic>\n                      and\n                      <jats:italic>DTYMK<\/jats:italic>\n                      cfRNA demonstrated high diagnostic accuracy between melanoma patients\u2019 and healthy donors\u2019 plasma (AUC &gt; 86%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001). cfRNA copies increased proportionally with increasing tumour burden independently of demographic variables and even remained elevated in individuals with radiological absence of disease. Re\u2010analysis of single\u2010cell transcriptomes revealed a pan\u2010tumour origin of cfRNA, including endothelial, cancer\u2010associated fibroblasts, macrophages and B cells beyond melanoma cells as cellular sources. Low baseline cfRNA levels were associated with significantly longer progression\u2010free survival (PFS) (\n                      <jats:italic>KPNA2<\/jats:italic>\n                      HR = .54,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0362;\n                      <jats:italic>DTL<\/jats:italic>\n                      HR = .60,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0349) and overall survival (\n                      <jats:italic>KPNA2<\/jats:italic>\n                      HR = .52,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0237;\n                      <jats:italic>BACE2<\/jats:italic>\n                      HR = .55,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0419;\n                      <jats:italic>DTYMK<\/jats:italic>\n                      HR = .43,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0393). Lastly, we found that cfRNA copies significantly increased during therapy in non\u2010responders compared to responders regardless of therapy and mutational subtypes and that the increase of\n                      <jats:italic>KPNA2<\/jats:italic>\n                      (HR = 1.73,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0441) and\n                      <jats:italic>DTYMK<\/jats:italic>\n                      (HR = 1.82,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.018) cfRNA during therapy was predictive of shorter PFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In sum, we identified a new panel of cfRNAs for a pan\u2010tumour liquid biopsy approach and demonstrated its utility as a prognostic, therapy\u2010monitoring tool independent of the melanoma mutational genotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1090","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:54:06Z","timestamp":1667350446000},"source":"Crossref","is-referenced-by-count":33,"title":["Circulating cell\u2010free messenger RNA enables non\u2010invasive pan\u2010tumour monitoring of melanoma therapy independent of the mutational genotype"],"prefix":"10.1002","volume":"12","author":[{"given":"Lea Jessica","family":"Albrecht","sequence":"first","affiliation":[{"name":"Department of Dermatology University Hospital of Essen West German Cancer Center University Duisburg\u2010Essen and the German Cancer Consortium (DKTK) Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"H\u00f6wner","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital of Essen West German Cancer Center University Duisburg\u2010Essen and the German Cancer 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