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. 2023 Jun 21;13(13):2131.
doi: 10.3390/diagnostics13132131.

Cell-Free Methylated PTGER4 and SHOX2 Plasma DNA as a Biomarker for Therapy Monitoring and Prognosis in Advanced Stage NSCLC Patients

Michael Fleischhacker  1 , Erkan Arslan  2 , Dana Reinicke  3 , Stefan Eisenmann  3 , Gerit Theil  3 , Jens Kollmeier  4 , Christoph Schäper  5 , Christian Grah  6 , Frank Klawonn  7   8 , Stefan Holdenrieder  9 , Bernd Schmidt  1
Affiliations

Cell-Free Methylated PTGER4 and SHOX2 Plasma DNA as a Biomarker for Therapy Monitoring and Prognosis in Advanced Stage NSCLC Patients

Michael Fleischhacker et al. Diagnostics (Basel). .

Abstract

Notwithstanding some improvement in the earlier detection of patients with lung cancer, most of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently utilized factors affecting the prognosis of lung cancer patients (stage, performance, and age), the recent application of biomarkers obtained by liquid profiling has gained more acceptance. In our study, we aimed to answer these questions: (i) Is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA a useful method for therapy monitoring, and is this also possible for patients treated with different therapy regimens? (ii) Is this approach possible when blood-drawing tubes, which allow for a delayed processing of blood samples, are utilized? Baseline values for mPTGER4 and mSHOX2 do not allow for clear discrimination between different response groups. In contrast, the combination of the methylation values for both genes shows a clear difference between responders vs. non-responders at the time of re-staging. Furthermore, blood drawing into tubes stabilizing the sample allows researchers more flexibility.

Keywords: liquid profiling; mPTGER4; mSHOX2; methylation; plasma.

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Conflict of interest statement

Michael Fleischhacker and Bernd Schmidt are coinventors of the patent: “Methods for assessing the treatment response of cancer patients and for treating cancer patients by analysing CpG methylation” (Application Number: 62076674, patent pending). There are no further patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all the publication policies on sharing data and materials.

Figures

Figure 1
Figure 1
Boxplots for the distribution of methylated PTGER4 (A–C) and SHOX2 (D–F) before the start of therapy (V1), at the time of first radiological staging (VS) and the ratio between both time points (VS/V1) for patients with partial remission (PR), stable disease (SD), and progressive disease (PD) in the staging exams.
Figure 2
Figure 2
Receiver-operating characteristic (ROC) curves (dark line) and respective 95% confidence intervals (CI; grey area) for the discrimination of patients with progressive disease (PD) from patients with no progression (stable disease + partial remission) for methylated PTGER4 (A–C) and SHOX2 (D–F) before start of therapy (V1), at time of first radiological staging (VS) and the ratio between both time points (VS/V1).
Figure 3
Figure 3
Receiver-operating characteristic (ROC) curves for the discrimination of patients with remission (PR) from patients with no remission (stable + progressive disease) for methylated PTGER4 (A–C) and SHOX2 (D–F) before start of therapy (V1), at time of first radiological staging (VS) and the ratio between both time points (VS/V1).
Figure 4
Figure 4
Decision-tree model using a combination of markers mSHOX2 ratio (VS/V1), mPTGER4 at staging (VS) and mPTGER4 ratio (VS/V1) for best prediction of therapy response. Patients with low mSHOX2 VS/V1 and low mPTGER4 VS had a high chance of achieving partial remission (R), whereas patients with high mSHOX2 VS/V1 and high mPTGER4 VS/V1 had a high probability for progressive disease (P). (A) shows the decision rules; and (B) the distribution of responses at every decision node.
Figure 5
Figure 5
Kaplan-Meier survival curves for the mSHOX2 at time of staging (VS) showing borderline longer survival for patients with low levels (green) than those with high levels (red).
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References

    1. Fois S.S., Paliogiannis P., Zinellu A., Fois A.G., Cossu A., Palmieri G. Molecular Epidemiology of the Main Druggable Genetic Alterations in Non-Small Cell Lung Cancer. Int. J. Mol. Sci. 2021;22:612. doi: 10.3390/ijms22020612. - DOI - PMC - PubMed
    1. S3-Leitlinie Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms. [(accessed on 28 February 2023)]. Available online: https://www.leitlinienprogramm-onkologie.de/leitlinien/lungenkarzinom/
    1. Mandel P., Metais P. Les Acides nucleiques du plasma sangiun chez l’Homme. C. R. Seances Soc. Biol. Fil. 1948;142:241–243. - PubMed
    1. Stroun M., Anker P., Maurice P., Gahan P.B. Circulating nucleic acids in higher organisms. Int. Rev. Cytol. 1977;51:1–48. - PubMed
    1. Stroun M., Anker P., Lyautey J., Lederrey C., Maurice P.A. Isolation and characterization of DNA from the plasma of cancer patients. Eur. J. Cancer Clin. Oncol. 1987;23:707–712. doi: 10.1016/0277-5379(87)90266-5. - DOI - PubMed

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