Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer

J. S. Ankeny; C. M. Court; S. Hou; Q. Li; M. Song; D. Wu; J. F. Chen; T. Lee; M. Lin; S. Sho; M. M. Rochefort; M. D. Girgis; J. Yao; Z. A. Wainberg; V. R. Muthusamy; R. R. Watson; T. R. Donahue; O. J. Hines; H. A. Reber; T. G. Graeber; H. R. Tseng; J. S. Tomlinson

doi:10.1038/bjc.2016.121

Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer

J. S. Ankeny, C. M. Court, S. Hou, Q. Li, M. Song, D. Wu, J. F. Chen, T. Lee, M. Lin, S. Sho, M. M. Rochefort, M. D. Girgis, J. Yao, Z. A. Wainberg, V. R. Muthusamy, R. R. Watson, T. R. Donahue, O. J. Hines, H. A. Reber, T. G. GraeberH. R. Tseng, J. S. Tomlinson

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118 Scopus citations

Abstract

Background:Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation.Methods:Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC.Results:We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ≥3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001).Conclusion:CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.

Original language	English (US)
Pages (from-to)	1367-1375
Number of pages	9
Journal	British Journal of Cancer
Volume	114
Issue number	12
DOIs	https://doi.org/10.1038/bjc.2016.121
State	Published - Jun 14 2016
Externally published	Yes

Bibliographical note

Funding Information:
The NanoVelcro Chips used in this research were supported by research grants (R33CA174562 and U01 CA198900) and an SBIR grant (R44 CA180482) from National Institute of Health.

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Ankeny, J. S., Court, C. M., Hou, S., Li, Q., Song, M., Wu, D., Chen, J. F., Lee, T., Lin, M., Sho, S., Rochefort, M. M., Girgis, M. D., Yao, J., Wainberg, Z. A., Muthusamy, V. R., Watson, R. R., Donahue, T. R., Hines, O. J., Reber, H. A., ... Tomlinson, J. S. (2016). Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer. British Journal of Cancer, 114(12), 1367-1375. https://doi.org/10.1038/bjc.2016.121

Ankeny, JS, Court, CM, Hou, S, Li, Q, Song, M, Wu, D, Chen, JF, Lee, T, Lin, M, Sho, S, Rochefort, MM, Girgis, MD, Yao, J, Wainberg, ZA, Muthusamy, VR, Watson, RR, Donahue, TR, Hines, OJ, Reber, HA, Graeber, TG, Tseng, HR & Tomlinson, JS 2016, 'Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer', British Journal of Cancer, vol. 114, no. 12, pp. 1367-1375. https://doi.org/10.1038/bjc.2016.121

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title = "Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer",

abstract = "Background:Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation.Methods:Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC.Results:We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ≥3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001).Conclusion:CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.",

author = "Ankeny, {J. S.} and Court, {C. M.} and S. Hou and Q. Li and M. Song and D. Wu and Chen, {J. F.} and T. Lee and M. Lin and S. Sho and Rochefort, {M. M.} and Girgis, {M. D.} and J. Yao and Wainberg, {Z. A.} and Muthusamy, {V. R.} and Watson, {R. R.} and Donahue, {T. R.} and Hines, {O. J.} and Reber, {H. A.} and Graeber, {T. G.} and Tseng, {H. R.} and Tomlinson, {J. S.}",

note = "Funding Information: The NanoVelcro Chips used in this research were supported by research grants (R33CA174562 and U01 CA198900) and an SBIR grant (R44 CA180482) from National Institute of Health.",

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T1 - Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer

AU - Ankeny, J. S.

AU - Court, C. M.

AU - Hou, S.

AU - Li, Q.

AU - Song, M.

AU - Wu, D.

AU - Chen, J. F.

AU - Lee, T.

AU - Lin, M.

AU - Sho, S.

AU - Rochefort, M. M.

AU - Girgis, M. D.

AU - Yao, J.

AU - Wainberg, Z. A.

AU - Muthusamy, V. R.

AU - Watson, R. R.

AU - Donahue, T. R.

AU - Hines, O. J.

AU - Reber, H. A.

AU - Graeber, T. G.

AU - Tseng, H. R.

AU - Tomlinson, J. S.

N1 - Funding Information: The NanoVelcro Chips used in this research were supported by research grants (R33CA174562 and U01 CA198900) and an SBIR grant (R44 CA180482) from National Institute of Health.

PY - 2016/6/14

Y1 - 2016/6/14

N2 - Background:Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation.Methods:Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC.Results:We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ≥3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001).Conclusion:CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.

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Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer

Abstract

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