Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(−)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during surgery. We found that the CTC count in PB but not IMV correlates with disease stages. Neoadjuvant chemotherapy did not lead to decreased CTC count in both types of blood samples. With cutoffs of four CTCs per 2 mL of blood, and serum carcinoembryonic antigen (CEA) level of 5 ng/mL, patients with non-metastatic disease were more likely to experience recurrence if they had high PB CTC count and high serum CEA concentration (odds ratio, 8.9). Our study demonstrates the feasibility of enumerating CTCs with a SACA chip in patients with colorectal cancer.
Highlights
Metastasis is the leading cause of cancer morbidity and mortality [1]
The self-assembled cell array (SACA) chip used in this experiment can detect one target cell spiked into 10,000,000 white blood
We found that the mean of circulating tumor cells (CTCs) count in the peripheral vein blood (PB) neoadjuvant chemotherapy (NAC)(−) group increased with disease stage (stage 0 to stage III; mean ± standard error of the mean (SEM) 4.0 ±1.7 to 6.3 ± 1.8, Figure 3A), while the same trend was not observed in the Inferior mesenteric vein (IMV) NAC(−) group (Figure 3B)
Summary
Circulating tumor cells (CTCs) are cells detached from an established tumor which enter the systemic circulation. A fraction of CTCs contain cancer-initiating cells that are capable of self-sustained survival and proliferation for establishing new foci of micrometastases in distal organs, and are thought to be an important mechanistic link for cancer metastasis [2]. Elevated CTC count is associated with shorter progression-free survival and overall survival in patients with metastatic breast cancer [3,4]. CTC is detected in the blood of patients with various solid tumors [5,6], and its numbers correlate to clinical stages, disease recurrence, tumor metastasis, treatment outcomes, and prognostic significance [7,8,9,10].
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