PHENOTYPIC AND GENETIC CHARACTERIZATION OF NON-SMALL CELL LUNG CANCER CIRCULATING TUMOR CELLS
Open Access
Author:
Nisic, Merisa
Graduate Program:
Molecular, Cellular and Integrative Biosciences
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 15, 2017
Committee Members:
Siyang Zheng, Dissertation Advisor/Co-Advisor Siyang Zheng, Committee Chair/Co-Chair Jian Yang, Committee Member Zhi-Chun Lai, Committee Member Andrea Marie Mastro, Outside Member
Keywords:
Circulating Tumor Cell Enrichment Microfiltration Lung Cancer
Abstract:
Circulating tumor cells (CTCs) are thought to be the drivers of metastasis, which is responsible for the majority of cancer-related deaths. CTCs have been established as a prognostic biomarker—higher CTC count correlates with worse clinical outcomes. Due to their one in a billion rarity, many biological and mechanistic aspects of circulating tumor cells remain unknown. This work describes the characterization of CTCs enriched using the Flexible Micro Spring Array (FMSA) system for label-free enrichment from whole blood. This research effort generated a single cell workflow from whole genome amplification (WGA) to next generation sequencing (NGS) using lung cancer cell lines. The aforementioned workflow was then used to genetically characterize single FMSA-enriched CTCs from clinical samples obtained from non-small cell lung cancer (NSCLC) patients. Higher CTC count was found to correlate to decreased cancer patient overall survival, thereby demonstrating the clinical relevance of FMSA enriched CTCs in non-small cell lung cancer. Further, four distinct phenotypic CTC subtypes were identified from NSCLC patient samples and higher heterogeneity of these subtypes correlated to decreased overall and progression-free survival.
