{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:50:03Z","timestamp":1791125403985,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T00:00:00Z","timestamp":1309219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell\u2010free DNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real\u2010time polymerase chain reaction was used to assess total cell\u2010free DNA (ring finger protein 185 [\n                      <jats:italic>RNF185<\/jats:italic>\n                      ]) and CpG island methylation of Ras association domain family member 1A (\n                      <jats:italic>RASSF1A<\/jats:italic>\n                      ) von Hippel\u2010Lindau (\n                      <jats:italic>VHL<\/jats:italic>\n                      ), prostaglandin\u2010endoperoxidase synthase 2 (\n                      <jats:italic>PTGS2<\/jats:italic>\n                      ), and\n                      <jats:italic>P16<\/jats:italic>\n                      (cyclin\u2010dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease\u2010specific survival were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Total cell\u2010free DNA levels and CpG island methylation of\n                      <jats:italic>RASSF1A<\/jats:italic>\n                      and\n                      <jats:italic>VHL<\/jats:italic>\n                      were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively.\n                      <jats:italic>VHL<\/jats:italic>\n                      methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes (\n                      <jats:italic>P<\/jats:italic>\n                      = .007). Total cell\u2010free DNA levels were higher in patients with metastatic RCC (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001) and necrotic RCC (\n                      <jats:italic>P<\/jats:italic>\n                      = .003) and were associated with poorer disease\u2010specific survival (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .001) and categorized total cell\u2010free DNA levels (\n                      <jats:italic>P<\/jats:italic>\n                      = .028) were retained as independent prognostic factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      The current results indicated that cell\u2010free DNA represents a novel serum\u2010based diagnostic and prognostic biomarker for RCC. Total serum cell\u2010free DNA levels and CpG island methylation of\n                      <jats:italic>RASSF1A<\/jats:italic>\n                      and\n                      <jats:italic>VHL<\/jats:italic>\n                      may be useful diagnostic biomarkers for RCC.\n                      <jats:italic>VHL<\/jats:italic>\n                      methylation of cell\u2010free DNA is suggestive of clear cell RCC. Total serum cell\u2010free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;. \u00a9 2011 American Cancer Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.26254","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T09:57:40Z","timestamp":1309427860000},"page":"82-90","source":"Crossref","is-referenced-by-count":94,"title":["Serum cell\u2010free DNA in renal cell carcinoma"],"prefix":"10.1002","volume":"118","author":[{"given":"Michela","family":"de Martino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Klatte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Haitel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Marberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00120-010-2342-4"},{"key":"e_1_2_6_4_2","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon SA","year":"1977","journal-title":"Cancer Res."},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2009.06.048"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2009.05.010"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2781"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.08289.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.02.106"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.01.038"},{"key":"e_1_2_6_11_2","first-page":"2785","article-title":"Cell\u2010free circulating DNA: diagnostic value in patients with renal cell cancer","volume":"30","author":"Hauser S","year":"2010","journal-title":"Anticancer Res."},{"key":"e_1_2_6_12_2","first-page":"1833","article-title":"Circulating cell\u2010free DNA in plasma\/serum of lung cancer patients as a potential screening and prognostic tool","volume":"52","author":"Pathak AK","year":"2006","journal-title":"Clin Chem."},{"key":"e_1_2_6_13_2","series-title":"Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs","first-page":"9","volume-title":"World Health Organization Classification of Tumours","author":"Reuter VE","year":"2004"},{"key":"e_1_2_6_14_2","first-page":"255","volume-title":"TNM Classification of Malignant Tumours","author":"Sobin LH","year":"2009"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198210000-00007"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2007.03.035"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1318.013"},{"key":"e_1_2_6_18_2","first-page":"1047","article-title":"Quantitative analysis of tumor\u2010derived methylated p16INK4a sequences in plasma, serum, and blood cells of hepatocellular carcinoma patients","volume":"9","author":"Wong IH","year":"2003","journal-title":"Clin Cancer Res."},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2446"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji237"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.148.3.6878708"},{"key":"e_1_2_6_22_2","volume-title":"Multivariate Analysis: A Practical Guide for Clinicians","author":"Katz MH","year":"1999"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64153-5"},{"key":"e_1_2_6_24_2","first-page":"1659","article-title":"DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells","volume":"61","author":"Jahr S","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24232"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.08.091"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20651"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4921"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2131"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2006.10.001"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.09.013"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25279"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24263"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.8345"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0786"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.11.032"},{"key":"e_1_2_6_37_2","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1093\/clinchem\/44.10.2201","article-title":"Use of real\u2010time quantitative PCR to compare DNA isolation methods","volume":"44","author":"de Kok JB","year":"1998","journal-title":"Clin Chem."},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0198-91"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.04.026"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.26254","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.26254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:12:19Z","timestamp":1760296339000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.26254"}},"subtitle":["A diagnostic and prognostic marker"],"short-title":[],"issued":{"date-parts":[[2011,6,28]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1002\/cncr.26254"],"URL":"https:\/\/doi.org\/10.1002\/cncr.26254","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,28]]}}}