Circulating tumor cells detected by lab-on-a-disc: Role in early diagnosis of gastric cancer

Hwa Mi Kang, Gwang Ha Kim, Hye Kyung Jeon, Dae Hwan Kim, Tae Yong Jeon, Do Youn Park, Hyunjin Jeong, Won Joo Chun, Mi-Hyun Kim, Juhee Park, Minji Lim, Tae-Hyeong Kim, Yoon-Kyung Cho, Hwa Mi Kang, Gwang Ha Kim, Hye Kyung Jeon, Dae Hwan Kim, Tae Yong Jeon, Do Youn Park, Hyunjin Jeong, Won Joo Chun, Mi-Hyun Kim, Juhee Park, Minji Lim, Tae-Hyeong Kim, Yoon-Kyung Cho

Abstract

Background: The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer.

Methods: A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique.

Results: After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level ≥2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level <2 per 7.5 mL of blood, 28 (62.2%) were healthy controls. Accordingly, the sensitivity and specificity for the differentiation of patients with gastric cancer from healthy controls were 85.3% and 90.3%, respectively. However, the presence of CTCs was not associated with any clinicopathologic features such as staging, histologic type, or mucin phenotype.

Conclusion: Although we could not prove the clinical feasibility of CTCs for gastric cancer staging, our results suggest a potential role of CTCs as an early diagnostic biomarker of gastric cancer.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Circulating tumor cells (CTCs).
Fig 1. Circulating tumor cells (CTCs).
CTCs were defined as captured cells that were CK+ or EpCAM+, CD45-, and DAPI+ and had a diameter >8 μm.
Fig 2. Circulating tumor cells (CTCs) in…
Fig 2. Circulating tumor cells (CTCs) in healthy controls and patients with gastric cancer.
CTCs were identified in 3 of 31 healthy controls and 105 of 116 patients with gastric cancer.
Fig 3. Receiver operating characteristic (ROC) curve.
Fig 3. Receiver operating characteristic (ROC) curve.
The value of circulating tumor cells (CTCs) showed an area under the ROC curve of 0.928 (95% confidence interval: 0.885–0.971, P < 0.001). To identify the optimal CTC threshold value for differentiating patients with gastric cancer from healthy controls, the sensitivity and specificity were optimized using a threshold count of 2 CTCs per 7.5 mL of blood.

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