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Multicenter Study
. 2017 Jun 13;18(6):1265.
doi: 10.3390/ijms18061265.

Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study

Yolanda Vidal Insua  1 , Juan de la Cámara  2 , Elena Brozos Vázquez  3 , Ana Fernández  4 , Francisca Vázquez Rivera  5 , Mª José Villanueva Villanueva Silva  6 , Jorge Barbazán  7 , Laura Muinelo-Romay  8   9 , Sonia Candamio Folgar  10 , Alicia Abalo  11   12 , Rafael López-López  13 , Miguel Abal  14 , Lorena Alonso-Alconada  15
Affiliations
Multicenter Study

Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study

Yolanda Vidal Insua et al. Int J Mol Sci. .

Abstract

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT) is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2) for detecting circulating tumor cells (CTCs) as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC) patients. Patients with higher gene panel expression before treatment had a reduced progression-free survival (PFS) and overall-survival (OS) rates compared with patients with low expression (p = 0.003 and p ≤ 0.001, respectively). Patients with increased expression of CTCs markers during treatment presented PFS and OS times of 8.95 and 11.74 months, respectively, compared with 14.41 and 24.7 for patients presenting decreased expression (PFS; p = 0.020; OS; p ≤ 0.001). Patients classified as non-responders by CTCs with treatment, but classified as responders by CT scan, showed significantly shorter survival times (PFS: 8.53 vs. 11.70; OS: 10.37 vs. 24.13; months). In conclusion, our CTCs detection panel demonstrated efficacy for early treatment response assessment in mCRC patients, and with increased reliability compared to CT scan.

Keywords: biomarkers; circulating tumor cells; metastatic colorectal cancer; therapy response.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Kaplan-Meier plots of progression-free survival (PFS) and overall survival (OS) according to high or low PrediCTC expression levels at baseline (A,B) and four weeks after treatment onset (C,D).
Figure 2
Figure 2
Kaplan-Meier curves showing progression-free survival (PFS) and overall survival (OS) based on the classification of patients as responders (Resp.) or non-responders (Non-Resp.) according to changes in circulating tumor cells (CTCs) gene expression levels with the treatment. (A) Classification of patients at the times of blood sample collection, according to PrediCTC. Kaplan-Meier curves for (B) PFS and (C) OS.
Figure 2
Figure 2
Kaplan-Meier curves showing progression-free survival (PFS) and overall survival (OS) based on the classification of patients as responders (Resp.) or non-responders (Non-Resp.) according to changes in circulating tumor cells (CTCs) gene expression levels with the treatment. (A) Classification of patients at the times of blood sample collection, according to PrediCTC. Kaplan-Meier curves for (B) PFS and (C) OS.
Figure 3
Figure 3
Kaplan-Meier curves showing progression-free survival (PFS) (A) and overall survival (OS) (B) according to the classification of a patient as responder (R) or non-responder (NR), based on the expression of the CTCs multimarker panel (CTC) and CT scan (CT).
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