Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

Hinz, Sebastian; Hendricks, Alexander; Wittig, Amke; Schafmayer, Clemens; Tepel, Jürgen; Kalthoff, Holger; Becker, Thomas; Röder, Christian

doi:10.1186/s12885-016-3035-1

Cited by 37 publications

(41 citation statements)

References 35 publications

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“…In our study, we now applied a refined quantitative real-time CK20- and EGFR-specific RT-qPCR. The overall detection rate of 53% for CK20 expression was significantly higher than with the up to now utilized nested RT-PCR in our work group [ 6 , 13 ]. In a representative cohort of CRC patients, the detection of CK20 expression within a CTC containing subset of PBMC presents a highly significant predictive marker in the prognosis of patients.…”

Section: Discussionmentioning

confidence: 75%

“…To date, various techniques for CTC detection have been presented [ 10 , 11 ]. Previously, we established a qualitative nested endpoint RT-PCR specific for cytokeratin (CK)20-mRNA, coding for an intermediate filament protein of epithelial cells, which has been shown to detect CTC within a fraction of peripheral blood mononuclear cells (PBMC) with a high specificity and sensitivity in the blood of CRC patients [ 12 , 13 ]. Thus, CK20 is a broadly accepted biomarker for the detection of CTC in patients suffering from CRC [ 6 , 12 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Identifying patients with an unfavorable prognosis in early stages of colorectal carcinoma

et al. 2018

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BackgroundIn recent years, the concept of liquid biopsy diagnostics in detection and progress monitoring of malignant diseases gained significant awareness. We here report on a semi-quantitative real-time cytokeratin 20 RT-PCR-based assay, for detecting circulating tumor cells within a fraction of peripheral blood mononuclear cells in colorectal cancer patients.MethodsIn total, 381 patients were included. Prior to surgical tumor resection, a peripheral blood sample was drawn. Mononuclear cells were isolated by Ficoll centrifugation and a cytokeratin 20 qRT-PCR assay was performed. Quantitative PCR data was assessed regarding histopathological characteristics and patients´ clinical outcome.ResultsA cut-off value was determined at ≥ 2.77 [EU]. Stratifying patients by this cut-off, it represents a statistically highly significant prognostic marker for both the overall and disease-free survival in the entire cohort UICC I-IV (both p<0.001) and in early tumor stages UICC I+II (overall survival p=0.003 and disease-free survival p=0.005). In multivariate analysis, the cut-off value stands for an independent predictor of significantly worse overall and disease-free survival (p=0.035 and p=0.047, respectively).ConclusionWe successfully established a highly sensitive real-time qRT-PCR assay by which we are able to identify colorectal cancer patients at risk for an unfavorable prognosis in UICC I and II stages.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Identifying patients with an unfavorable prognosis in early stages of colorectal carcinoma

et al. 2018

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“…CTCs have gained considerable attention in recent years as reliable biomarkers for tumour diagnosis, prognosis and real‐time monitoring of drug resistance. In addition, CTC isolation from liquid biopsies is a reproducible and minimally invasive technique . The US Food and Drug Administration approved CellSearch system can only capture E‐CTCs (using ferrofluids loaded with anti‐EpCAM antibodies ) and not the M‐CTCs and E/M‐CTCs that have lost epithelial markers .…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of epithelial–mesenchymal transition typing of circulating tumour cells in colorectal cancer

2020

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AimThe aim was to determine the diagnostic value of epithelial-mesenchymal transition typing of circulating tumour cells (CTCs) in colorectal cancer (CRC).Method Peripheral blood samples were collected from 51 CRC patients before anti-tumour treatment from April 2016 to June 2018 at the Peking University Shenzhen Hospital. The blood samples were analysed using the CanPatrol CTC typing technique (SurExam, Guangzhou, China), which combines nanomembrane enrichment with mRNA in situ hybridization. Based on the marker expression, the CTCs were classified into epithelial, epithelial mesenchymal and mesenchymal (M-CTC) types. The correlation between the CTC counts and clinicopathological characteristics such as gender, age, TNM stage, lymph node metastasis and distant metastasis were analysed by univariate and multivariate Cox regression models. The overall survival and progression-free survival (PFS) of patients demarcated by CTC typing were analysed using the Kaplan-Meier method and log-rank tests.Result M-CTCs were detected more frequently in patients with lymph node metastasis (N2 81.8%; N1 72.7%; N0 38.9%) as well as distant metastasis (M0 50%; M1a 81.25%; M1b 85.7%) compared to those without metastasis. In addition, the presence of M-CTCs was significantly correlated with distant metastasis (P < 0.01). Univariate analysis showed that lymph node metastasis (P = 0.035), distant metastasis (P < 0.001) and total CTC count ≥ 4 (P = 0.007) and M-CTC count ≥ 1 (P < 0.001) were significantly associated with unfavourable PFS, and lymph node metastasis (P = 0.04), distant metastasis (P = 0.01) and M-CTC count ≥ 1 (P < 0.001) were significantly associated with unfavourable overall survival. Multivariate analysis showed that the presence of M-CTCs was the only independent prognostic factor for poor PFS, and patients with M-CTCs had significantly shorter PFS than those without (P = 0.011).Conclusion M-CTCs are significantly associated with CRC severity and metastasis, and M-CTC count is an independent predictor of prognosis.

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“…In recent years, CTCs have been considered as a liquid biopsy for all solid tumors. The technique of isolation and analyzation of CTCs has been shown to be a highly repeatable, and minimally invasive technique for diagnosis, prognosis, and real-time monitoring of drug resistance for cancer treatment [18,19]. Previous studies have indicated that CTCs are closely associated with the biological behavior of tumor.…”

Section: Discussionmentioning

confidence: 99%

Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients

Wang

Zhou

Zhang

et al. 2019

Int J Colorectal Dis

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Purpose This study aimed to evaluate the prognostic value of circulating tumor cells (CTCs) in advanced colorectal cancer (CRC) patients during chemotherapy course. Methods From January 2016 to September 2017, the clinicopathological variables, such as gender, age, tumor location, tumor de-differentiation, depth of invasion, lymphatic invasion, distant metastasis, TNM stage, CTCs enumeration during 2-6 cycles of chemotherapy, and serum carcinoembryonic antigen (CEA) level during the same period, of 121 newly acquired and histopathologically confirmed CRC patients were collected from the Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. All patients were followed up for survival until the end of November 2018. Statistical analysis focused on the associations between CTCs counts and clinicopathological variables. Overall survival (OS) and progression-free survival (PFS) among different prognostic factors were calculated using the Kaplan-Meier method, and the differences between the survival curves were compared by using the log-rank test. Factors of prognostic significance were investigated with the multivariate Cox regression analysis. Results Here, 71 of 121 patients were CTC-positive, in which CTC-positive rate was positively correlated with the depth of invasion, lymphatic invasion, distant metastasis, TNM stage, and serum CEA level (P < 0.05 for all). However, no significant difference was found between CTC-positive and other clinicopathological variables (P > 0.05 for all), such as gender, age, tumor location, and tumor de-differentiation. CTCs counts gradually increased with the advancement of depth of invasion (P = 0.002), lymphatic invasion (P = 0.004), distant metastasis (P = 0.007), TNM stage (P = 0.001), serum CEA level (P = 0.001), and decreased tumor de-differentiation (P = 0.011). Furthermore, the Kaplan-Meier survival curves showed that patients with CTC-positive had a significantly unfavorable PFS (14 vs. 23 months, P = 0.001) and OS (18 vs. 25 months, P = 0.003). The multivariate Cox regression analyses revealed that the presence of CTCs during chemotherapy was an independent factor for unfavorable PFS (hazard ratio (HR) 2.682, P = 0.017, 95% confidence interval (CI) 1.193-6.029) and OS (HR 2.790, P = 0.048, 95% CI 1.010-7.705) in advanced CRC patients. Conclusions This study provided an evidence that the presence of CTCs may be valuable for predicting survival outcome, and CTCs was associated with unfavorable survival in advanced CRC patients during chemotherapy.

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Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

Cited by 37 publications

References 35 publications

Identifying patients with an unfavorable prognosis in early stages of colorectal carcinoma

Identifying patients with an unfavorable prognosis in early stages of colorectal carcinoma

Clinical significance of epithelial–mesenchymal transition typing of circulating tumour cells in colorectal cancer

Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients

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