Abstract
At initial diagnosis, most patients with small-cell lung cancer (SCLC) present with metastatic disease with a high number of tumor cells (CTCs) circulating in the blood. We analyzed RNA transcripts specific for neuroendocrine and for epithelial cell lineages, and Notch pathway delta-like 3 ligand (DLL3), the actionable target of rovalpituzumab tesirine (Rova-T) in CTC samples. Peripheral blood samples from 48 SCLC patients were processed using the microfluidic Parsortix™ technology to enrich the CTCs. Blood samples from 26 healthy donors processed in the same way served as negative controls. The isolated cells were analyzed for the presence of above-mentioned transcripts using quantitative PCR. In total, 16/51 (31.4%) samples were CTC-positive as determined by the expression of epithelial cell adhesion molecule 1 (EpCAM), cytokeratin 19 (CK19), chromogranin A (CHGA), and/or synaptophysis (SYP). The epithelial cell lineage-specific EpCAM and/or CK19 gene expression was observed in 11 (21.6%) samples, and positivity was not associated with impaired survival. The neuroendocrine cell lineage-specific CHGA and/or SYP were positive in 13 (25.5%) samples, and positivity was associated with poor overall survival. DLL3 transcripts were observed in four (7.8%) SCLC blood samples and DLL3-positivity was similarly associated with poor overall survival (OS). CTCs in SCLC patients can be assessed using epithelial and neuroendocrine cell lineage markers at the molecular level. Thus, the implementation of liquid biopsy may improve the management of lung cancer patients, in terms of a faster diagnosis, patient stratification, and on-treatment therapy monitoring.
Highlights
Lung cancer is the most common cancer worldwide
Two major types of lung cancer exist: non-small-cell lung cancer (NSCLC), which accounts for about 85% of all lung cancer cases, and small-cell lung cancer (SCLC), which is diagnosed in approximately 15% of all lung cancers
Thirty-four patients died within the observation period, with a median overall survival of 7 months
Summary
Lung cancer is the most common cancer worldwide. In 2018, a total of 2.1 million new cases were estimated, accounting for 11.6% of all new cancer diagnoses [1,2]. Two major types of lung cancer exist: non-small-cell lung cancer (NSCLC), which accounts for about 85% of all lung cancer cases, and small-cell lung cancer (SCLC), which is diagnosed in approximately 15% of all lung cancers. SCLC, is usually diagnosed rather late when the cancer has already disseminated. In this case a multimodal therapy which includes chemotherapy and radiotherapy is considered the gold standard [3]. Due to these different therapeutic approaches, it is of utmost importance to have a reliable diagnostic platform to differentiate between
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