Dataset Information

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.

SUBMITTER: Ankeny JS

PROVIDER: S-EPMC4984454 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Ankeny J S JS Court C M CM Hou S S Li Q Q Song M M Wu D D Chen J F JF Lee T T Lin M M Sho S S Rochefort M M MM Girgis M D MD Yao J J Wainberg Z A ZA Muthusamy V R VR Watson R R RR Donahue T R TR Hines O J OJ Reber H A HA Graeber T G TG Tseng H R HR Tomlinson J S JS

British journal of cancer 20160601 12

<h4>Background</h4>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.<h4>Methods</h4>Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for ...[more]

PMID: 27300108

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Project description:BackgroundMost cancer deaths are caused by metastases, resulting from circulating tumor cells (CTC) that detach from the primary cancer and survive in distant organs. The aim of the present study was to develop a CTC gene signature and to assess its prognostic relevance after surgery for pancreatic ductal adenocarcinoma (PDAC).MethodsNegative depletion fluorescence activated cell sorting (FACS) was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumour (T), and non-tumoural pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. 'Ingenuity Pathway Analysis' software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS).ResultsUsing stringent statistical analysis, we retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway, TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were overexpressed in CTC. High co-expression of TGF-β1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 6 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 - 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 - 1.861)).ConclusionsPancreatic CTC isolated from blood samples using FACS-based negative depletion, express a cell motility gene signature. Expression of this newly defined cell motility gene signature in the primary tumour can predict survival of patients undergoing surgical resection for pancreatic cancer.Trial registrationClinical trials.gov NCT00495924.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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