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Selected Works of Shu-Ching Chang, PhD, MS
Article
Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy.
Clinical chemistry
  • Selena Y Lin, Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA, USA
  • Shu-Ching Chang, Medical Data Research Center, Providence Health & Services, Portland, OR, USA
  • Stella Lam, Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, Santa Monica, CA.
  • Romela Irene Ramos, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA
  • Kevin Tran, Division of Molecular Oncology, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.
  • Shuichi Ohe, Department of Translational Molecular Medicine, John Wayne Cancer Institute, Saint John's Health Center, PHS, Santa Monica, CA.
  • Matthew P Salomon, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.
  • Ali Asgar S Bhagat
  • Chwee Teck Lim
  • Trevan D Fischer, Department of Surgical Oncology, John Wayne Cancer Institute, PHS, Santa Monica, CA.
  • Leland J Foshag, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA
  • Christine L Boley, Department of Immuno-Oncology and Clinical Research, John Wayne Cancer Institute, PHS, Santa Monica, CA.
  • Steven J O'Day, The John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA
  • Dave Hoon, The John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA
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Document Type
Article
Publication Date
1-1-2020
Keywords
  • Aged,
  • Antibodies, Monoclonal, Humanized,
  • Biomarkers, Tumor,
  • Disease-Free Survival,
  • Female,
  • Humans,
  • Immunotherapy,
  • Kaplan-Meier Estimate,
  • Male,
  • Melanoma,
  • Middle Aged,
  • Neoplasm Staging,
  • Neoplastic Cells, Circulating,
  • Proportional Hazards Models,
  • Prospective Studies,
  • Proto-Oncogene Proteins B-raf,
  • RNA, Messenger,
  • Risk Factors,
  • Up-Regulation,
  • beta Catenin
Disciplines
Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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-mutation 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

CONCLUSIONS: CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.

Clinical Institute
Cancer
Department
Oncology
Department
Surgery
Citation Information
Selena Y Lin, Shu-Ching Chang, Stella Lam, Romela Irene Ramos, et al.. "Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy." Clinical chemistry (2020)
Available at: http://works.bepress.com/shu-ching-chang/47/