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Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis
Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966103/ https://www.ncbi.nlm.nih.gov/pubmed/35370397 http://dx.doi.org/10.1177/11772719221088404 |
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author | Gunderson, Camille C Radhakrishnan, Rangasudhagar Gomathinayagam, Rohini Husain, Sanam Aravindan, Sheeja Moore, Kathleen M Dhanasekaran, Danny N Jayaraman, Muralidharan |
author_facet | Gunderson, Camille C Radhakrishnan, Rangasudhagar Gomathinayagam, Rohini Husain, Sanam Aravindan, Sheeja Moore, Kathleen M Dhanasekaran, Danny N Jayaraman, Muralidharan |
author_sort | Gunderson, Camille C |
collection | PubMed |
description | Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 “poor” (<6 months progression free interval [PFI]) and 22 “favorable” (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients. |
format | Online Article Text |
id | pubmed-8966103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-89661032022-03-31 Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis Gunderson, Camille C Radhakrishnan, Rangasudhagar Gomathinayagam, Rohini Husain, Sanam Aravindan, Sheeja Moore, Kathleen M Dhanasekaran, Danny N Jayaraman, Muralidharan Biomark Insights Original Research Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 “poor” (<6 months progression free interval [PFI]) and 22 “favorable” (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients. SAGE Publications 2022-03-28 /pmc/articles/PMC8966103/ /pubmed/35370397 http://dx.doi.org/10.1177/11772719221088404 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Gunderson, Camille C Radhakrishnan, Rangasudhagar Gomathinayagam, Rohini Husain, Sanam Aravindan, Sheeja Moore, Kathleen M Dhanasekaran, Danny N Jayaraman, Muralidharan Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title | Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title_full | Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title_fullStr | Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title_full_unstemmed | Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title_short | Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis |
title_sort | circulating tumor cell-free dna genes as prognostic gene signature for platinum resistant ovarian cancer diagnosis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966103/ https://www.ncbi.nlm.nih.gov/pubmed/35370397 http://dx.doi.org/10.1177/11772719221088404 |
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