Cancer Diagnosis Program | Biorepositories and Biospecimen Research Branch

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Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer.

Author(s): Onstenk W, Sieuwerts AM, Mostert B, Lalmahomed Z, Bolt-de Vries JB, van Galen A, Smid M, Kraan J, Van M, de Weerd V, Ramírez-Moreno R, Biermann K, Verhoef C, Grünhagen DJ, IJzermans JN, Gratama JW, Martens JW, Foekens JA, Sleijfer S

Publication: Oncotarget, 2016, Vol. 7, Page 59058-59069

PubMed ID: 27340863 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study compared the gene expression profiles of CTCs isolated by CellSearch with those from case-matched FFPE primary tumor and metastatic tissue specimens. Peripheral blood (30 mL) was collected in CellSave and EDTA tubes from 23 patients with metastatic colorectal cancer just prior to liver surgery and processed within 24 h. Red blood cells were removed by a modified Ficoll density gradient and CTCs were isolated and enumerated using the CellSearch method. RNA was isolated from CTCs using the Qiagen AllPrep DNA/RNA Micro Kit. RNA was isolated using the High- Pure RNA Paraffin Kit from FFPE primary tumor and liver metastasis tissues with ≥30% tumor cells. Twenty-five CTC-specific genes were measured by real-time RT-qPCR and expression levels were normalized to three reference genes (GUSB, HMBS, and HPRT1).

   Summary of Findings:

   Primary tumor and metastasis gene expression profiles were concordant in 16/23 patients (70%). CTC gene expression profiles were concordant with the liver metastasis in 17/23 patients (74%) and with the primary tumor in 13/23 patients (57%). Gene expression profiles of CTCs more closely resembled those from the liver metastasis in 13 patients and the primary tumor in five patients, but reflected characteristics from both the primary tumor and the liver metastasis in three patients, and did not resemble either the primary tumor nor the liver metastasis in two patients. Levels of concordance were not affected by time of metastasis presentation (synchronous or metachronous), number of metastases, chemotherapy, or patient age or gender. Only FCGBP was significantly downregulated in the liver metastases compared to the primary tumor (P=0.004) and CDH1, CDH17, CDX1, CEACAM5, FABP1, FCGBP, IGFBP3, IGFBP4, and MAPT were significantly downregulated in CTCs (P=0.001-0.03). Similarly, CDH1, CDH17, CDX1, CEACAM5, FABP1, IGFBP3, and MAPT were significantly downregulated in CTCs compared to liver metastases (P=0.001-0.02).

   Biospecimens

   • Bodily Fluid - Blood
   • Tissue - Liver
   • Tissue - Colorectal

   Preservative Types

   • Formalin
   • Other Preservative

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   RNA	Real-time qRT-PCR
   Cell count/volume	Fluorescent microscopy

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Number of metastases Synchronous metastasis presentation Metachronous metastasis presentation Chemotherapy No chemotherapy
   Preaquisition	Patient age	68 ± 10 years
   Real-time qRT-PCR Specific	Targeted nucleic acid	AGR2 AKR1C3 CDH1 CDH17 CDH5 CDX1 CEACAM5 COL4A1 CXCL1 FABP1 FCGBP GPX2 IGFBP3 IGFBP4 IGFBP5 KRT19 KRT20 LAD1 MACROD1 MAPT PRSS8 RARRES2 S100P TRIM2 TSPAN8 GUSB HMBS HPRT1
   Preaquisition	Patient gender	Female Male
   Biospecimen Acquisition	Biospecimen location	Primary colorectal tumor Liver metastasis Circulating tumor cell

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