The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer
Abstract Background CT scans are used in routine clinical practice for the diagnosis and treatment surveillance of non‐small cell lung cancer (NSCLC). However, more sensitive methods are desirable. Liquid biopsy analyses of RNA and DNA can offer more sensitive diagnostic approaches. Cell‐free RNA (c...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-08-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.14540 |
| _version_ | 1818507715038674944 |
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| author | Martin Metzenmacher Balazs Hegedüs Jan Forster Alexander Schramm Peter A. Horn Christoph A. Klein Nicola Bielefeld Till Ploenes Clemens Aigner Jens T. Siveke Martin Schuler Smiths S. Lueong |
| author_facet | Martin Metzenmacher Balazs Hegedüs Jan Forster Alexander Schramm Peter A. Horn Christoph A. Klein Nicola Bielefeld Till Ploenes Clemens Aigner Jens T. Siveke Martin Schuler Smiths S. Lueong |
| author_sort | Martin Metzenmacher |
| collection | DOAJ |
| description | Abstract Background CT scans are used in routine clinical practice for the diagnosis and treatment surveillance of non‐small cell lung cancer (NSCLC). However, more sensitive methods are desirable. Liquid biopsy analyses of RNA and DNA can offer more sensitive diagnostic approaches. Cell‐free RNA (cfRNA) has been described in several malignancies, but its clinical utility has not previously been explored. Methods We evaluated the clinical utility of cfRNA for early detection and surveillance of tumor disease in a proof‐of‐concept study. Using real‐time‐droplet digital polymerase chain reaction we characterized a candidate transcript (MORF4L2) in plasma samples from 41 advanced stage, 38 early stage NSCLC and 39 healthy samples. We compared its diagnostic performance with tumor markers and evaluated its utility for disease monitoring. Results MORF4L2 cfRNA was more abundant in patients than in healthy donors (p < 0.0001). Using the Youden index approach (cutoff value of 537 copies/ml was established) with a sensitivity of 0.73 (95% CI: 0.61–0.82) and a specificity of 0.87 (95% CI: 0.73–0.96). Positive and negative predictive values of 0.92 (95% CI: 0.83–0.95) and 0.59 (95% CI: 0.47–0.83) were achieved. Combination of cfRNA and Cyfra21‐1 improved its predictive value from 89.5% to 94.7%. Low baseline MORF4L2 levels were associated with better overall survival (HR:0.25, 95% CI: 0.09–0.7, p = 0.009) and progression‐free survival for patients treated with tyrosine kinase inhibitors (p = 0.011) and chemotherapy (p = 0.019). MORF4L2 profile between baseline and follow‐up mirrored radiological response and tumor dynamics better than tumor markers. cfRNA transcripts allowed monitoring tumor dynamics in patients without tumor‐reported genetic alterations. Conclusion Our data support clinical utility of cfRNA for detection and surveillance of NSCLC. Further studies with larger cohorts are required. |
| first_indexed | 2024-12-10T22:21:54Z |
| format | Article |
| id | doaj.art-2636748d7c9c455babf6ed2f5ee009ba |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-12-10T22:21:54Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-2636748d7c9c455babf6ed2f5ee009ba2022-12-22T01:31:17ZengWileyThoracic Cancer1759-77061759-77142022-08-0113152180219110.1111/1759-7714.14540The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancerMartin Metzenmacher0Balazs Hegedüs1Jan Forster2Alexander Schramm3Peter A. Horn4Christoph A. Klein5Nicola Bielefeld6Till Ploenes7Clemens Aigner8Jens T. Siveke9Martin Schuler10Smiths S. Lueong11Department of Medical Oncology West German Cancer Center, University Hospital Essen Essen GermanyDepartment of Thoracic Surgery West German Cancer Center, University Medicine Essen Ruhrlandklinik, University Duisburg‐Essen Essen GermanyGerman Cancer Consortium (DKTK), Partner site University Hospital Essen Essen GermanyLaboratory for Molecular Oncology, Department of Medical Oncology West German Cancer Center, University Hospital Essen, University of Duisburg‐Essen Essen GermanyInstitute for Transfusion Medicine, University Hospital Essen Essen GermanyExperimental Medicine and Therapy Research, University of Regensburg Regensburg GermanyGerman Cancer Consortium (DKTK), Partner site University Hospital Essen Essen GermanyDepartment of Thoracic Surgery West German Cancer Center, University Medicine Essen Ruhrlandklinik, University Duisburg‐Essen Essen GermanyDepartment of Thoracic Surgery West German Cancer Center, University Medicine Essen Ruhrlandklinik, University Duisburg‐Essen Essen GermanyGerman Cancer Consortium (DKTK), Partner site University Hospital Essen Essen GermanyDepartment of Medical Oncology West German Cancer Center, University Hospital Essen Essen GermanyGerman Cancer Consortium (DKTK), Partner site University Hospital Essen Essen GermanyAbstract Background CT scans are used in routine clinical practice for the diagnosis and treatment surveillance of non‐small cell lung cancer (NSCLC). However, more sensitive methods are desirable. Liquid biopsy analyses of RNA and DNA can offer more sensitive diagnostic approaches. Cell‐free RNA (cfRNA) has been described in several malignancies, but its clinical utility has not previously been explored. Methods We evaluated the clinical utility of cfRNA for early detection and surveillance of tumor disease in a proof‐of‐concept study. Using real‐time‐droplet digital polymerase chain reaction we characterized a candidate transcript (MORF4L2) in plasma samples from 41 advanced stage, 38 early stage NSCLC and 39 healthy samples. We compared its diagnostic performance with tumor markers and evaluated its utility for disease monitoring. Results MORF4L2 cfRNA was more abundant in patients than in healthy donors (p < 0.0001). Using the Youden index approach (cutoff value of 537 copies/ml was established) with a sensitivity of 0.73 (95% CI: 0.61–0.82) and a specificity of 0.87 (95% CI: 0.73–0.96). Positive and negative predictive values of 0.92 (95% CI: 0.83–0.95) and 0.59 (95% CI: 0.47–0.83) were achieved. Combination of cfRNA and Cyfra21‐1 improved its predictive value from 89.5% to 94.7%. Low baseline MORF4L2 levels were associated with better overall survival (HR:0.25, 95% CI: 0.09–0.7, p = 0.009) and progression‐free survival for patients treated with tyrosine kinase inhibitors (p = 0.011) and chemotherapy (p = 0.019). MORF4L2 profile between baseline and follow‐up mirrored radiological response and tumor dynamics better than tumor markers. cfRNA transcripts allowed monitoring tumor dynamics in patients without tumor‐reported genetic alterations. Conclusion Our data support clinical utility of cfRNA for detection and surveillance of NSCLC. Further studies with larger cohorts are required.https://doi.org/10.1111/1759-7714.14540cfRNAddPCRliquid biopsyNGSNSCLC |
| spellingShingle | Martin Metzenmacher Balazs Hegedüs Jan Forster Alexander Schramm Peter A. Horn Christoph A. Klein Nicola Bielefeld Till Ploenes Clemens Aigner Jens T. Siveke Martin Schuler Smiths S. Lueong The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer Thoracic Cancer cfRNA ddPCR liquid biopsy NGS NSCLC |
| title | The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer |
| title_full | The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer |
| title_fullStr | The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer |
| title_full_unstemmed | The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer |
| title_short | The clinical utility of cfRNA for disease detection and surveillance: A proof of concept study in non‐small cell lung cancer |
| title_sort | clinical utility of cfrna for disease detection and surveillance a proof of concept study in non small cell lung cancer |
| topic | cfRNA ddPCR liquid biopsy NGS NSCLC |
| url | https://doi.org/10.1111/1759-7714.14540 |
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