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Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients

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Abstract

Background

The rarity of circulating tumour cells (CTCs) in peripheral blood requires the application of sensitive techniques for their detection. The aim of our study was to (i) first determine the sensitivity of cytokeratin-7 (KRT7) mRNA expression levels for the molecular detection of CTCs using spiked-in lung adenocarcinoma (AC)-derived A549 cells and (ii) evaluate the impact of KRT7 mRNA expression in peripheral whole blood on the response to treatment and prognosis of patients with advanced lung AC who were treated with first-line platinum-based chemotherapy.

Methods

A549 cells were micro-manipulated before being spiked into whole blood samples obtained from healthy donors. Additionally, whole blood samples from 65 lung AC patients were collected in PAXgene blood tubes before the start of first-line platinum-based chemotherapy. KRT7 mRNA expression was measured using RT-qPCR.

Results

Through the spike-in experiment we found that it is feasible to detect a single A549 tumour cell in 2.5 ml whole blood and that the KRT7 mRNA levels were linearly correlated with the number of spiked-in tumour cells with a high reproducibility. In lung AC patients, no significant differences in response rate to chemotherapy, progression-free survival or overall survival and KRT7 mRNA levels were found.

Conclusions

Our data show that KRT7 mRNA expression measured by RT-qPCR serves as a sensitive approach for the molecular detection of KRT7-positive CTC-resembling A549 cells in peripheral whole blood. The KRT7 mRNA levels measured were not significantly associated with the response to chemotherapy or the survival of patients with advanced lung AC. Additional studies are required to establish the possible clinical significance of KRT7 mRNA expression in whole blood after chemotherapy.

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Acknowledgments

This work was funded by Slovenian Research Agency Grant J3-4076.

Conflicts of interest

The authors declare they have no conflicts of interest.

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Authors and Affiliations

  1. University Clinic Golnik, Golnik 36, 4204, Golnik, Slovenia

    Ana Koren, Eva Sodja, Matija Rijavec, Peter Korosec & Tanja Cufer

  2. Blood Transfusion Centre of Slovenia, Slajmerjeva 6, 1000, Ljubljana, Slovenia

    Mojca Jez

  3. Institute of Oncology Ljubljana, Zaloska cesta 2, 1000, Ljubljana, Slovenia

    Viljem Kovac

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  1. Ana Koren
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Koren, A., Sodja, E., Rijavec, M. et al. Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients. Cell Oncol. 38, 387–395 (2015). https://doi.org/10.1007/s13402-015-0238-4

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