Clinical Significance of TWIST-Positive Circulating Tumor Cells in Patients with Esophageal Squamous Cell Carcinoma
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Background/Aims: Unlike other gastrointestinal tract cancers, there are relatively few reports on the clinical significance of circulating tumor cells (CTCs) and TWIST, a marker of epithelial-mesenchymal transition, in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the clinical significance of TWIST expression in CTCs in patients with ESCC. Methods: Peripheral blood samples for CTC analyses were prospectively obtained from 52 patients with ESCC prior to treatment between September 2017 and September 2019. CTCs were detected using a centrifugal microfluidic system based on a fluid-assisted separation technique, and CTCs positive for TWIST on immunostaining were defined as TWIST (+) CTCs. Results: Of the 52 patients with ESCC, CTCs and TWIST (+) CTCs were detected in 44 patients (84.6%) and 39 patients (75.0%), respectively. The CTC and TWIST (+) CTC counts were significantly higher in patients aged >65 years and those who had a large tumor (>3 cm) than in those aged ≤65 years and those who had a small tumor (≤3 cm), respectively. There were no differences in CTC and TWIST (+) CTC counts according to tumor location, histologic grade, or TNM stage. TWIST (+) CTCs were significantly associated with histologic grade; a proportion of TWIST (+) CTCs ≥0.5 was significantly associated with advanced histologic grade. Other clinicopathologic characteristics such as sex, age, tumor location, tumor size, and TNM stages were not significantly associated with TWIST (+) CTCs. Conclusions: Our study showed that TWIST (+) CTCs were frequently detected in patients with ESCC, and a high proportion of TWIST (+) CTCs was associated with poor differentiation.
Abstract
Background/Aims: Unlike other gastrointestinal tract cancers, there are relatively few reports on the clinical significance of circulating tumor cells (CTCs) and TWIST, a marker of epithelial-mesenchymal transition, in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the clinical significance of TWIST expression in CTCs in patients with ESCC. Methods: Peripheral blood samples for CTC analyses were prospectively obtained from 52 patients with ESCC prior to treatment between September 2017 and September 2019. CTCs were detected using a centrifugal microfluidic system based on a fluid-assisted separation technique, and CTCs positive for TWIST on immunostaining were defined as TWIST (+) CTCs. Results: Of the 52 patients with ESCC, CTCs and TWIST (+) CTCs were detected in 44 patients (84.6%) and 39 patients (75.0%), respectively. The CTC and TWIST (+) CTC counts were significantly higher in patients aged >65 years and those who had a large tumor (>3 cm) than in those aged ≤65 years and those who had a small tumor (≤3 cm), respectively. There were no differences in CTC and TWIST (+) CTC counts according to tumor location, histologic grade, or TNM stage. TWIST (+) CTCs were significantly associated with histologic grade; a proportion of TWIST (+) CTCs ≥0.5 was significantly associated with advanced histologic grade. Other clinicopathologic characteristics such as sex, age, tumor location, tumor size, and TNM stages were not significantly associated with TWIST (+) CTCs. Conclusions: Our study showed that TWIST (+) CTCs were frequently detected in patients with ESCC, and a high proportion of TWIST (+) CTCs was associated with poor differentiation.
참고문헌 (32)
- Ferlay J, "Cancer incidence and mortality worldwide : sources, methods and major patterns in GLOBOCAN 2012", Int J Cancer, 136, pp.E359~ (2015)
- 정혜경, "식도암의 국내 현황 및 병인", Korean Journal of Helicobacter Upper Gastrointestinal Research, 19(3), pp.145~148 (2019), 대한상부위장관ㆍ헬리코박터학회[DOI]
- Wu T, "Clinical applications of circulating tumor cells in pharmacotherapy : challenges and perspectives", Mol Pharmacol, 92, pp.232~239 (2017)
- Qiao Y, "Prognostic value of circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma", Onco Targets Ther, 10, pp.1363~1373 (2017)
- Han L, "Clinical significance of tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma", Medicine(Baltimore), 98, pp.e13921~ (2019)
- Chen W, "Practical value of identifying circulating tumor cells to evaluate esophageal squamous cell carcinoma staging and treatment efficacy", Thorac Cancer, 9, pp.956~966 (2018)
- Reeh M, "Circulating tumor cells as a biomarker for preoperative prognostic staging in patients with esophageal cancer", Ann Surg, 261, pp.1124~1130 (2015)
- Su PJ, "Circulating tumour cells as an independent prognostic factor in patients with advanced oesophageal squamous cell carcinoma undergoing chemoradiotherapy", Sci Rep, 6, pp.31423~ (2016)
- Kaganoi J, "Detection of circulating oesophageal squamous cancer cells in peripheral blood and its impact on prognosis", Br J Surg, 91, pp.1055~1060 (2004)
- Xu HT, "Prognostic value of circulating tumor cells in esophageal cancer", World J Gastroenterol, 23, pp.1310~1318 (2017)
- Shah AK, "Early diagnostic biomarkers for esophageal adenocarcinoma : the current state of play", Cancer Epidemiol Biomarkers Prev, 22, pp.1185~1209 (2013)
- 전혜경, "위암에서 순환종양세포의 임상적 의의", Korean Journal of Helicobacter Upper Gastrointestinal Research, 18(3), pp.162~167 (2018), 대한상부위장관ㆍ헬리코박터학회[DOI]
- 강은아, "액체 생검(Liquid Biopsy): 위암 및 헬리코박터 감염증에서 적응과 전망", Korean Journal of Helicobacter Upper Gastrointestinal Research, 18(3), pp.150~156 (2018), 대한상부위장관ㆍ헬리코박터학회[DOI]
- Kang HM, "Circulating tumor cells detected by lab-on-a-disc : role in early diagnosis of gastric cancer", PLoS One, 12, pp.e0180251~ (2017)
- Moon Won Lee, "Clinical Application of Circulating Tumor Cells in Gastric Cancer", Gut and Liver, 13(4), pp.394~401 (2019), 거트앤리버 소화기연관학회협의회[DOI]
- Han D, "Detection of epithelialmesenchymal transition status of circulating tumor cells in patients with esophageal squamous carcinoma", Biomed Res Int, 2018, pp.7610154~ (2018)
- Yang J, "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis", Cell, 117, pp.927~939 (2004)
- Gao Y, "Relationship between TWIST expression and epithelial-mesenchymal transition of oesophageal squamous cell carcinoma", Cell Biol Int, 36, pp.571~577 (2012)
- Xie F, "Twist, an independent prognostic marker for predicting distant metastasis and survival rates of esophageal squamous cell carcinoma patients", Clin Exp Metastasis, 26, pp.1025~1032 (2009)
- Yuen HF, "Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis", J Clin Pathol, 60, pp.510~514 (2007)
- 임민지, "순환종양세포 검출 기술", Korean Journal of Helicobacter Upper Gastrointestinal Research, 18(3), pp.157~161 (2018), 대한상부위장관ㆍ헬리코박터학회[DOI]
- Kim TH, "FAST : size-selective, clog-free isolation of rare cancer cells from whole blood at a liquidliquid interface", Anal Chem, 89, pp.1155~1162 (2017)
- Lee A, "All-in-one centrifugal microfluidic device for size-selective circulating tumor cell isolation with high purity", Anal Chem, 86, pp.11349~11356 (2014)
- Choi MK, "Circulating tumor cells detected using fluid-assisted separation technique in esophageal squamous cell carcinoma", J Gastroenterol Hepatol, 34, pp.552~560 (2019)
- Li M, "Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer", Biomed Res Int, 2014, pp.981261~ (2014)
- Amin MB, "AJCC Cancer Staging Manual" (2017), Springer
- Blum Murphy M, "Pathological complete response in patients with esophageal cancer after the trimodality approach : the association with baseline variables and survival : The University of Texas MD Anderson Cancer Center experience", Cancer, 123, pp.4106~4113 (2017)
- Gong T, "Nuclear expression of Twist promotes lymphatic metastasis in esophageal squamous cell carcinoma", Cancer Biol Ther, 13, pp.606~613 (2012)
- Nakajima TE, "Nucleostemin and TWIST as predictive markers for recurrence after neoadjuvant chemotherapy for esophageal carcinoma", Cancer Sci, 103, pp.233~238 (2012)
- Sasaki K, "Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma", J Exp Clin Cancer Res, 28, pp.158~ (2009)
- Balakrishnan A, "Circulating tumor cell cluster phenotype allows monitoring response to treatment and predicts survival", Sci Rep, 9, pp.7933~ (2019)
- Van Vliet EP, "Staging investigations for oesophageal cancer : a meta-analysis", Br J Cancer, 98, pp.547~557 (2008)