The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia

Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy child...

Full description

Bibliographic Details
Main Authors: Martina Wahlund, Indranil Sinha, Kristina Broliden, Shanie Saghafian-Hedengren, Anna Nilsson, Anna Berggren
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/15/5305
id doaj-198809e73f444ee29e81933c1573651c
record_format Article
spelling doaj-198809e73f444ee29e81933c1573651c2020-11-25T02:46:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-01215305530510.3390/ijms21155305The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile NeutropeniaMartina Wahlund0Indranil Sinha1Kristina Broliden2Shanie Saghafian-Hedengren3Anna Nilsson4Anna Berggren5Department of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, SwedenChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 76 Stockholm, SwedenDepartment of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, SwedenChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 76 Stockholm, SwedenChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 76 Stockholm, SwedenDepartment of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, SwedenInfection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (<i>n</i> = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis.https://www.mdpi.com/1422-0067/21/15/5305transcriptomeinfectionchildrenneutropenia
collection DOAJ
language English
format Article
sources DOAJ
author Martina Wahlund
Indranil Sinha
Kristina Broliden
Shanie Saghafian-Hedengren
Anna Nilsson
Anna Berggren
spellingShingle Martina Wahlund
Indranil Sinha
Kristina Broliden
Shanie Saghafian-Hedengren
Anna Nilsson
Anna Berggren
The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
International Journal of Molecular Sciences
transcriptome
infection
children
neutropenia
author_facet Martina Wahlund
Indranil Sinha
Kristina Broliden
Shanie Saghafian-Hedengren
Anna Nilsson
Anna Berggren
author_sort Martina Wahlund
title The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
title_short The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
title_full The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
title_fullStr The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
title_full_unstemmed The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
title_sort feasibility of host transcriptome profiling as a diagnostic tool for microbial etiology in childhood cancer patients with febrile neutropenia
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-07-01
description Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (<i>n</i> = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis.
topic transcriptome
infection
children
neutropenia
url https://www.mdpi.com/1422-0067/21/15/5305
work_keys_str_mv AT martinawahlund thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT indranilsinha thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT kristinabroliden thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT shaniesaghafianhedengren thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT annanilsson thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT annaberggren thefeasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT martinawahlund feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT indranilsinha feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT kristinabroliden feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT shaniesaghafianhedengren feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT annanilsson feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
AT annaberggren feasibilityofhosttranscriptomeprofilingasadiagnostictoolformicrobialetiologyinchildhoodcancerpatientswithfebrileneutropenia
_version_ 1724759079310589952