{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:39:52Z","timestamp":1778539192197,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T00:00:00Z","timestamp":1595721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","award":["11111"],"award-info":[{"award-number":["11111"]}],"id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Groschinsky Memory Foundation","award":["1111"],"award-info":[{"award-number":["1111"]}]},{"name":"The Swedish Society of Medicine","award":["1111"],"award-info":[{"award-number":["1111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (n = 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.<\/jats:p>","DOI":"10.3390\/ijms21155305","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T04:39:50Z","timestamp":1595824790000},"page":"5305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia"],"prefix":"10.3390","volume":"21","author":[{"given":"Martina","family":"Wahlund","sequence":"first","affiliation":[{"name":"Department of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Clinical Microbiology, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2513-5927","authenticated-orcid":false,"given":"Indranil","family":"Sinha","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Broliden","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanie","family":"Saghafian-Hedengren","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Astrid Lindgren Children\u2019s Hospital, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Berggren","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Infectious Disease Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1200\/JCO.2016.71.7017","article-title":"Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update","volume":"35","author":"Lehrnbecher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e219","DOI":"10.1097\/INF.0000000000000326","article-title":"A prospective multicenter study of microbiologically defined infections in pediatric cancer patients with fever and neutropenia: Swiss Pediatric Oncology Group 2003 fever and neutropenia study","volume":"33","author":"Agyeman","year":"2014","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jcv.2009.11.026","article-title":"Respiratory viruses, a common microbiological finding in neutropenic children with fever","volume":"47","author":"Lindblom","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1086\/522533","article-title":"A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation","volume":"45","author":"Castagnola","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1097\/INF.0000000000001209","article-title":"Respiratory viral infections and coinfections in children with cancer, fever and neutropenia: Clinical outcome of infections caused by different respiratory viruses","volume":"35","author":"Torres","year":"2016","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1177\/0009922812456736","article-title":"Nasopharyngeal detection of respiratory viruses in febrile neutropenic children","volume":"51","author":"Suryadevara","year":"2012","journal-title":"Clin. Pediatr. (Phila)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1542\/peds.2013-3042","article-title":"Clinical utility of PCR for common viruses in acute respiratory illness","volume":"133","author":"Rhedin","year":"2014","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Soderman, M., Rhedin, S., Tolfvenstam, T., Rotzen-Ostlund, M., Albert, J., Broliden, K., and Lindblom, A. (2016). Frequent respiratory viral infections in children with febrile neutropenia\u2014A prospective follow-up study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157398"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.coi.2006.11.003","article-title":"Principles of intracellular viral recognition","volume":"19","author":"Saito","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.chom.2009.07.006","article-title":"Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans","volume":"6","author":"Zaas","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12792","DOI":"10.1073\/pnas.1302968110","article-title":"Gene expression profiles in febrile children with defined viral and bacterial infection","volume":"110","author":"Hu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1001\/jama.2016.11236","article-title":"Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children","volume":"316","author":"Herberg","year":"2016","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/jama.2016.9207","article-title":"Association of RNA biosignatures with bacterial infections in febrile infants aged 60 days or younger","volume":"316","author":"Mahajan","year":"2016","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kelly, R.S., Lasky-Su, J., Yeung, S.J., Stone, R.M., Caterino, J.M., Hagan, S.C., Lyman, G.H., Baden, L.R., Glotzbecker, B.E., and Coyne, C.J. (2018). Integrative omics to detect bacteremia in patients with febrile neutropenia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197049"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"328","DOI":"10.7326\/0003-4819-64-2-328","article-title":"Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia","volume":"64","author":"Bodey","year":"1966","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.paed.2019.12.002","article-title":"Febrile neutropenia in paediatric oncology","volume":"30","author":"Davis","year":"2020","journal-title":"Paediatr. Child Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/cncr.29833","article-title":"Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia","volume":"122","author":"Hakim","year":"2016","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1097\/INF.0b013e31825c4b7e","article-title":"Frequency and clinical outcome of respiratory viral infections and mixed viral-bacterial infections in children with cancer, fever and neutropenia","volume":"31","author":"Torres","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1164\/rccm.201504-0749OC","article-title":"Rhinovirus detection in symptomatic and asymptomatic children: Value of host transcriptome analysis","volume":"193","author":"Heinonen","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1093\/infdis\/jiy608","article-title":"Host gene expression in nose and blood for the diagnosis of viral respiratory infection","volume":"219","author":"Yu","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8043","DOI":"10.1038\/s41598-018-26239-1","article-title":"A 2-transcript host cell signature distinguishes viral from bacterial diarrhea and it is influenced by the severity of symptoms","volume":"8","author":"Salas","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1128\/JCM.01057-16","article-title":"Host-based peripheral blood gene expression analysis for diagnosis of infectious diseases","volume":"55","author":"Holcomb","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11780","DOI":"10.1038\/s41598-019-48162-9","article-title":"A qPCR expression assay of IFI44L gene differentiates viral from bacterial infections in febrile children","volume":"9","author":"Pischedda","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Marotta, C., Di Gennaro, F., Pizzol, D., Madeira, G., Monno, L., Saracino, A., Putoto, G., Casuccio, A., and Mazzucco, W. (2018). The at risk child clinic (ARCC): 3 years of health activities in support of the most vulnerable children in Beira, Mozambique. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15071350"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/jmv.21368","article-title":"Development and implementation of a molecular diagnostic platform for daily rapid detection of 15 respiratory viruses","volume":"81","author":"Gupta","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1101\/gr.092759.109","article-title":"Circos: An information aesthetic for comparative genomics","volume":"19","author":"Krzywinski","year":"2009","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5305\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:51Z","timestamp":1760176311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,26]]},"references-count":26,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155305"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155305","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,26]]}}}