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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...

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Autores principales: Gunderson, Camille C, Radhakrishnan, Rangasudhagar, Gomathinayagam, Rohini, Husain, Sanam, Aravindan, Sheeja, Moore, Kathleen M, Dhanasekaran, Danny N, Jayaraman, Muralidharan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
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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.
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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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