{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:31:09Z","timestamp":1779103869130,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100012505","name":"Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012505","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA167967-01A1"],"award-info":[{"award-number":["1R01CA167967-01A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)\/DNA biomarker panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III\/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF\u2013mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (P = 0.03) and overall survival (P = 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (CTNNB1) overexpression (P &amp;lt;0.01) compared to nondisease donor blood. CTC-CTNNB1 was associated with progressive disease\/stable disease compared to complete-responder patient status (P = 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment\/follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>CTC-derived mRNA\/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.<\/jats:p><\/jats:sec>","DOI":"10.1373\/clinchem.2019.307140","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T21:16:40Z","timestamp":1572556600000},"page":"169-177","source":"Crossref","is-referenced-by-count":26,"title":["Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy"],"prefix":"10.1093","volume":"66","author":[{"given":"Selena Y","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, Santa Monica, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Ching","family":"Chang","sequence":"additional","affiliation":[{"name":"Medical Data Research Center, Providence Saint Joseph Health, Portland, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stella","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, Santa Monica, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romela","family":"Irene Ramos","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, Santa Monica, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, 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