The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.

Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 y...

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Autores principales:	Mie Jareid, Igor Snapkov, Marit Holden, Lill-Tove Rasmussen Busund, Eiliv Lund, Therese Haugdahl Nøst
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1883ecafdf4144bd8332af1b81cbbca1
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spelling	oai:doaj.org-article:1883ecafdf4144bd8332af1b81cbbca12021-12-02T20:19:25ZThe blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.1932-620310.1371/journal.pone.0256442https://doaj.org/article/1883ecafdf4144bd8332af1b81cbbca12021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256442https://doaj.org/toc/1932-6203Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 years before diagnosis. For this, we used RNA-stabilized whole blood, which contains circulating immune cells, from a sample of EOC cases from the population-based Norwegian Women and Cancer (NOWAC) postgenome cohort. We explored case-control differences in gene expression in all EOC (66 case-control pairs), as well as associations between gene expression and metastatic EOC (56 pairs), serous EOC (45 pairs, 44 of which were metastatic), and interval from blood sample collection to diagnosis (≤3 or >3 years; 34 and 31 pairs, respectively). Lastly, we assessed differential expression of genes associated with EOC in published functional genomics studies that used blood samples collected from newly diagnosed women. After adjustment for multiple testing, this nested case-control study revealed no significant case-control differences in gene expression in all EOC (false discovery rate q>0.96). With the exception of a few probes, the log2 fold change values obtained in gene-wise linear models were below ±0.2. P-values were lowest in analyses of metastatic EOC (80% of which were serous EOC). No common transcriptional profile was indicated by interval to diagnosis; when comparing the 100 genes with the lowest p-values in gene-wise tests in samples collected ≤3 and >3 years before EOC diagnosis, no overlap in these genes was observed. Among 86 genes linked to ovarian cancer in previous publications, our data contained expression values for 42, and of these, tests of LIME1, GPR162, STAB1, and SKAP1, resulted in unadjusted p<0.05. Although limited by sample size, our findings indicated less variation in blood gene expression between women with similar tumor characteristics.Mie JareidIgor SnapkovMarit HoldenLill-Tove Rasmussen BusundEiliv LundTherese Haugdahl NøstPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256442 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mie Jareid Igor Snapkov Marit Holden Lill-Tove Rasmussen Busund Eiliv Lund Therese Haugdahl Nøst The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
description	Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 years before diagnosis. For this, we used RNA-stabilized whole blood, which contains circulating immune cells, from a sample of EOC cases from the population-based Norwegian Women and Cancer (NOWAC) postgenome cohort. We explored case-control differences in gene expression in all EOC (66 case-control pairs), as well as associations between gene expression and metastatic EOC (56 pairs), serous EOC (45 pairs, 44 of which were metastatic), and interval from blood sample collection to diagnosis (≤3 or >3 years; 34 and 31 pairs, respectively). Lastly, we assessed differential expression of genes associated with EOC in published functional genomics studies that used blood samples collected from newly diagnosed women. After adjustment for multiple testing, this nested case-control study revealed no significant case-control differences in gene expression in all EOC (false discovery rate q>0.96). With the exception of a few probes, the log2 fold change values obtained in gene-wise linear models were below ±0.2. P-values were lowest in analyses of metastatic EOC (80% of which were serous EOC). No common transcriptional profile was indicated by interval to diagnosis; when comparing the 100 genes with the lowest p-values in gene-wise tests in samples collected ≤3 and >3 years before EOC diagnosis, no overlap in these genes was observed. Among 86 genes linked to ovarian cancer in previous publications, our data contained expression values for 42, and of these, tests of LIME1, GPR162, STAB1, and SKAP1, resulted in unadjusted p<0.05. Although limited by sample size, our findings indicated less variation in blood gene expression between women with similar tumor characteristics.
format	article
author	Mie Jareid Igor Snapkov Marit Holden Lill-Tove Rasmussen Busund Eiliv Lund Therese Haugdahl Nøst
author_facet	Mie Jareid Igor Snapkov Marit Holden Lill-Tove Rasmussen Busund Eiliv Lund Therese Haugdahl Nøst
author_sort	Mie Jareid
title	The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
title_short	The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
title_full	The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
title_fullStr	The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
title_full_unstemmed	The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.
title_sort	blood transcriptome prior to ovarian cancer diagnosis: a case-control study in the nowac postgenome cohort.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1883ecafdf4144bd8332af1b81cbbca1
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The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.

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