Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary research

Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy

Authors: Dejun Zhang, Lei Zhao, Pengfei Zhou, Hong Ma, Fang Huang, Min Jin, Xiaomeng Dai, Xiumei Zheng, Shaoyi Huang, Tao Zhang

Published in: Cancer Cell International | Issue 1/2017

Login to get access

Abstract

Background

Circulating tumor cells (CTCs) detected in peripheral blood (PB) of cancer patients can be identified as isolated CTCs and circulating tumor microemboli (CTM). This study aimed to evaluate the prognostic value of CTM detection and CTC phenotype in advanced colorectal cancer (CRC) patients during chemotherapy.

Methods

A size-based platform for CTC isolation was applied. PB samples (5 ml) from 98 advanced CRC patients during 2–6 cycles chemotherapy were collected for CTC detection, and CTC count was correlated to patient’s clinicopathological characteristics and clinical outcome. And CTC phenotype was measured by immunofluorescent staining and evaluate the predictive significance on survival in 32 CTCs-positive patients with advanced CRC.

Results

Forty-eight of 98 patients were CTCs-positive, including 18 CTM-positive patients, and CTC detection was positively correlated with lymphatic invasion (P = 0.049), TNM stage (P = 0.023), and serum CEA level (P = 0.014). Moreover, Kaplan–Meier survival and Cox regression analyses revealed that the presence of CTCs was an independent factor for poor PFS and OS (P < 0.05) in advanced CRC patients during chemotherapy, and CTM-positive patients had shooter survival than isolated CTCs-positive patients (P < 0.05). Furthermore, patients with vimentin+ isolated CTCs/CTM had shorter PFS and OS compared with CK+ CTCs (P < 0.05).

Conclusions

This study provided evidence that the presence of CTCs was positively correlated with poor prognosis, and furthermore, CTM and vimentin+ CTCs predicted poorer survival, which indicated that CTM and vimentin+ CTCs detected by a sensitive platform could be used to improve prognostic value of CTCs in advanced CRC patients under treatment.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
Hazama S, Nakamura Y, Tanaka H, Hirakawa K, Tahara K, Shimizu R, et al. A phase II study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). J Transl Med. 2014;12:108.CrossRefPubMedPubMedCentral
3.
Matsusaka S, Chin K, Ogura M, Suenaga M, Shinozaki E, Mishima Y, et al. Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer. Cancer Sci. 2010;101(4):1067–71.CrossRefPubMed
4.
Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol. 2009;20(7):1223–9.CrossRefPubMed
5.
Sastre J, Maestro ML, Gomez-Espana A, Rivera F, Valladares M, Massuti B, et al. Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Oncologist. 2012;17(7):947–55.CrossRefPubMedPubMedCentral
6.
Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.CrossRefPubMed
7.
Tol J, Koopman M, Miller MC, Tibbe A, Cats A, Creemers GJ, et al. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Ann Oncol. 2010;21(5):1006–12.CrossRefPubMed
8.
Torino F, Bonmassar E, Bonmassar L, De Vecchis L, Barnabei A, Zuppi C, et al. Circulating tumor cells in colorectal cancer patients. Cancer Treat Rev. 2013;39(7):759–72.CrossRefPubMed
9.
Rao CG, Chianese D, Doyle GV, Miller MC, Russell T, Sanders RA Jr, et al. Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors. Int J Oncol. 2005;27(1):49–57.PubMed
10.
Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20(5):576–90.CrossRefPubMedPubMedCentral
11.
Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.CrossRefPubMed
12.
Bednarz-Knoll N, Alix-Panabieres C, Pantel K. Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev. 2012;31(3–4):673–87.CrossRefPubMed
13.
Gorges TM, Tinhofer I, Drosch M, Rose L, Zollner TM, Krahn T, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.CrossRefPubMedPubMedCentral
14.
Sastre J, Maestro ML, Puente J, Veganzones S, Alfonso R, Rafael S, et al. Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables. Ann Oncol. 2008;19(5):935–8.CrossRefPubMed
15.
Bork U, Rahbari NN, Scholch S, Reissfelder C, Kahlert C, Buchler MW, et al. Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study. Br J Cancer. 2015;112(8):1306–13.CrossRefPubMedPubMedCentral
16.
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol. 2000;156(1):57–63.CrossRefPubMedPubMedCentral
17.
Hofman V, Long E, Ilie M, Bonnetaud C, Vignaud JM, Flejou JF, et al. Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method. Cytopathology. 2012;23(1):30–8.CrossRefPubMed
18.
Hofman VJ, Ilie MI, Bonnetaud C, Selva E, Long E, Molina T, et al. Cytopathologic detection of circulating tumor cells using the isolation by size of epithelial tumor cell method: promises and pitfalls. Am J Clin Pathol. 2011;135(1):146–56.CrossRefPubMed
19.
Lianidou ES, Markou A, Strati A. The role of CTCs as tumor biomarkers. Adv Exp Med Biol. 2015;867:341–67.CrossRefPubMed
20.
Pantel K, Alix-Panabieres C. Real-time liquid biopsy in cancer patients: fact or fiction? Cancer Res. 2013;73(21):6384–8.CrossRefPubMed
21.
Small AC, Gong Y, Oh WK, Hall SJ, van Rijn CJ, Galsky MD. The emerging role of circulating tumor cell detection in genitourinary cancer. J Urol. 2012;188(1):21–6.CrossRefPubMed
22.
23.
Huang X, Gao P, Song Y, Sun J, Chen X, Zhao J, et al. Meta-analysis of the prognostic value of circulating tumor cells detected with the Cell Search System in colorectal cancer. BMC Cancer. 2015;15:202.CrossRefPubMedPubMedCentral
24.
Huang X, Gao P, Song Y, Sun J, Chen X, Zhao J, et al. Relationship between circulating tumor cells and tumor response in colorectal cancer patients treated with chemotherapy: a meta-analysis. BMC Cancer. 2014;14:976.CrossRefPubMedPubMedCentral
25.
Li H, Song P, Zou B, Liu M, Cui K, Zhou P, et al. Circulating tumor cell analyses in patients with esophageal squamous cell carcinoma using epithelial marker-dependent and -independent approaches. Medicine (Baltimore). 2015;94(38):e1565.CrossRefPubMedPubMedCentral
26.
Farace F, Massard C, Vimond N, Drusch F, Jacques N, Billiot F, et al. A direct comparison of Cell Search and ISET for circulating tumour-cell detection in patients with metastatic carcinomas. Br J Cancer. 2011;105(6):847–53.CrossRefPubMedPubMedCentral
27.
Hofman V, Ilie MI, Long E, Selva E, Bonnetaud C, Molina T, et al. Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the Cell Search Assay and the isolation by size of epithelial tumor cell method. Int J Cancer. 2011;129(7):1651–60.CrossRefPubMed
28.
Vona G, Estepa L, Beroud C, Damotte D, Capron F, Nalpas B, et al. Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology. 2004;39(3):792–7.CrossRefPubMed
29.
De Giorgi V, Pinzani P, Salvianti F, Panelos J, Paglierani M, Janowska A, et al. Application of a filtration- and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma. J Invest Dermatol. 2010;130(10):2440–7.CrossRefPubMed
30.
Tsai WS, Chen JS, Shao HJ, Wu JC, Lai JM, Lu SH, et al. Circulating tumor cell count correlates with colorectal neoplasm progression and is a prognostic marker for distant metastasis in non-metastatic patients. Sci Rep. 2016;6:24517.CrossRefPubMedPubMedCentral
31.
Das A, Kunkel M, Joudeh J, Dicker DT, Scicchitano A, Allen JE, et al. Clinico-pathological correlation of serial measurement of circulating tumor cells in 24 metastatic colorectal cancer patients receiving chemotherapy reveals interpatient heterogeneity correlated with CEA levels but independent of KRAS and BRAF mutation. Cancer Biol Ther. 2015;16(5):709–13.CrossRefPubMedPubMedCentral
32.
Hardingham JE, Grover P, Winter M, Hewett PJ, Price TJ, Thierry B. Detection and clinical significance of circulating tumor cells in colorectal cancer—20 years of progress. Mol Med. 2015;21(Suppl 1):S25–31.CrossRefPubMedPubMedCentral
33.
de Albuquerque A, Kubisch I, Stolzel U, Ernst D, Boese-Landgraf J, Breier G, et al. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients. J Transl Med. 2012;10:222.CrossRefPubMedPubMedCentral
34.
Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, et al. Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer. J Clin Oncol. 2011;29(12):1547–55.CrossRefPubMed
35.
Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012;30(5):525–32.CrossRefPubMed
36.
Long E, Ilie M, Bence C, Butori C, Selva E, Lalvee S, et al. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness. Cancer Med. 2016;5(6):1022–30.CrossRefPubMedPubMedCentral
37.
Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol. 2014;25(8):1506–16.CrossRefPubMed
38.
van de Stolpe A, Pantel K, Sleijfer S, Terstappen LW, den Toonder JM. Circulating tumor cell isolation and diagnostics: toward routine clinical use. Cancer Res. 2011;71(18):5955–60.CrossRefPubMed
39.
Camara O, Rengsberger M, Egbe A, Koch A, Gajda M, Hammer U, et al. The relevance of circulating epithelial tumor cells (CETC) for therapy monitoring during neoadjuvant (primary systemic) chemotherapy in breast cancer. Ann Oncol. 2007;18(9):1484–92.CrossRefPubMed
40.
Barbazan J, Muinelo-Romay L, Vieito M, Candamio S, Diaz-Lopez A, Cano A, et al. A multimarker panel for circulating tumor cells detection predicts patient outcome and therapy response in metastatic colorectal cancer. Int J Cancer. 2014;135(11):2633–43.CrossRefPubMed
Metadata
Title
Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy
Authors
Dejun Zhang
Lei Zhao
Pengfei Zhou
Hong Ma
Fang Huang
Min Jin
Xiaomeng Dai
Xiumei Zheng
Shaoyi Huang
Tao Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0373-7

Other articles of this Issue 1/2017

Cancer Cell International 1/2017 Go to the issue

Primary Research

Secretory phospholipase-A2 and fatty acid composition in oral reactive lesions: a cross-sectional study

Primary Research

The human, F-actin-based cytoskeleton as a mutagen sensor

Primary research

Human basonuclin 2 up-regulates a cascade set of interferon-stimulated genes with anti-cancerous properties in a lung cancer model

Primary Research

Hypoxia and TGF-β1 induced PLOD2 expression improve the migration and invasion of cervical cancer cells by promoting epithelial-to-mesenchymal transition (EMT) and focal adhesion formation

Retraction Note

Retraction Note: Long noncoding RNA ANRIL is activated by hypoxia-inducible factor-1α and promotes osteosarcoma cell invasion and suppresses cell apoptosis upon hypoxia

Primary Research

Restoration of miR-29b exerts anti-cancer effects on glioblastoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits