Cargando…

Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer

BACKGROUND: Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities. METHODS: We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients. We a...

Descripción completa

Detalles Bibliográficos
Autores principales: Tarabichi, M, Saiselet, M, Trésallet, C, Hoang, C, Larsimont, D, Andry, G, Maenhaut, C, Detours, V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430711/
https://www.ncbi.nlm.nih.gov/pubmed/25965298
http://dx.doi.org/10.1038/bjc.2014.665
_version_ 1782371223730126848
author Tarabichi, M
Saiselet, M
Trésallet, C
Hoang, C
Larsimont, D
Andry, G
Maenhaut, C
Detours, V
author_facet Tarabichi, M
Saiselet, M
Trésallet, C
Hoang, C
Larsimont, D
Andry, G
Maenhaut, C
Detours, V
author_sort Tarabichi, M
collection PubMed
description BACKGROUND: Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities. METHODS: We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients. We also included patient-matched non-cancerous thyroid and lymph node samples as controls to address some limits of previous studies. RESULTS: The transcriptomes of patient-matched primary tumours and metastases were more similar than those of unrelated metastases/primary pairs, as previously reported in other organ systems. This similarity partly reflected patient background. Lymphoid tissues in the metastases confounded the comparison of patient-matched primary tumours and metastases. We circumvented this with an original data adjustment, revealing a differential expression of stroma-related gene signatures also regulated in other organs. The comparison of N0 vs N+ primary tumours uncovered a signal irreproducible across independent data sets. This signal was also detectable when comparing the non-cancerous thyroid tissues adjacent to N0 and N+ tumours, suggesting a cohort-specific bias also likely present in previous similarly sized studies. Classification of N0 vs N+ yielded an accuracy of 63%, but additional statistical controls absent in previous studies revealed that this is explainable by chance alone. We used large data sets from The Cancer Genome Atlas: N0 vs N+ classification was not better than random for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. CONCLUSIONS: The clinical potential of gene expression to predict nodal metastases seems limited for most cancers.
format Online
Article
Text
id pubmed-4430711
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-44307112016-05-12 Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer Tarabichi, M Saiselet, M Trésallet, C Hoang, C Larsimont, D Andry, G Maenhaut, C Detours, V Br J Cancer Full Paper BACKGROUND: Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities. METHODS: We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients. We also included patient-matched non-cancerous thyroid and lymph node samples as controls to address some limits of previous studies. RESULTS: The transcriptomes of patient-matched primary tumours and metastases were more similar than those of unrelated metastases/primary pairs, as previously reported in other organ systems. This similarity partly reflected patient background. Lymphoid tissues in the metastases confounded the comparison of patient-matched primary tumours and metastases. We circumvented this with an original data adjustment, revealing a differential expression of stroma-related gene signatures also regulated in other organs. The comparison of N0 vs N+ primary tumours uncovered a signal irreproducible across independent data sets. This signal was also detectable when comparing the non-cancerous thyroid tissues adjacent to N0 and N+ tumours, suggesting a cohort-specific bias also likely present in previous similarly sized studies. Classification of N0 vs N+ yielded an accuracy of 63%, but additional statistical controls absent in previous studies revealed that this is explainable by chance alone. We used large data sets from The Cancer Genome Atlas: N0 vs N+ classification was not better than random for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. CONCLUSIONS: The clinical potential of gene expression to predict nodal metastases seems limited for most cancers. Nature Publishing Group 2015-05-12 2015-05-12 /pmc/articles/PMC4430711/ /pubmed/25965298 http://dx.doi.org/10.1038/bjc.2014.665 Text en Copyright © 2015 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Full Paper
Tarabichi, M
Saiselet, M
Trésallet, C
Hoang, C
Larsimont, D
Andry, G
Maenhaut, C
Detours, V
Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title_full Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title_fullStr Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title_full_unstemmed Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title_short Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
title_sort revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer
topic Full Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430711/
https://www.ncbi.nlm.nih.gov/pubmed/25965298
http://dx.doi.org/10.1038/bjc.2014.665
work_keys_str_mv AT tarabichim revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT saiseletm revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT tresalletc revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT hoangc revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT larsimontd revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT andryg revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT maenhautc revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer
AT detoursv revisitingthetranscriptionalanalysisofprimarytumoursandassociatednodalmetastaseswithenhancedbiologicalandstatisticalcontrolsapplicationtothyroidcancer