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Article: Gene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization

TitleGene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization
Authors
KeywordsTransarterial Chemoembolization
hepatocellular carcinoma
precision oncology
gene signature
treatment response
Issue Date2019
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm
Citation
International Journal of Biological Sciences, 2019, v. 15 n. 12, p. 2654-2663 How to Cite?
AbstractTransarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naïve tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE. TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p<0.0001). In addition, multivariable Cox model demonstrates that TACE Navigator was independently associated with survival (HR: 9.31, 95% CI: 3.46-25.0, p<0.001). In our validation cohorts, the association between TACE Navigator and survival remained robust in both Asian patients who received adjuvant TACE (Hong Kong: 60 months vs 25.6 months p=0.007; Shandong: 61.3 months vs 32.1 months, p=0.027) and European patients who received TACE as primary therapy (Mainz: 60 months vs 41.5 months, p=0.041). These results indicate that a TACE-specific molecular classifier is robust in predicting TACE response. This gene signature can be used to identify patients who will have the greatest survival benefit after TACE treatment and enable personalized treatment modalities for patients with HCC.
Persistent Identifierhttp://hdl.handle.net/10722/281897
ISSN
2017 Impact Factor: 4.057
2015 SCImago Journal Rankings: 1.927
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorFako, V-
dc.contributor.authorMartin, SP-
dc.contributor.authorPomyen, Y-
dc.contributor.authorBudhu, A-
dc.contributor.authorChaisaingmongkol, J-
dc.contributor.authorFranck, S-
dc.contributor.authorLee, JM-F-
dc.contributor.authorNg, IO-L-
dc.contributor.authorCheung, T-T-
dc.contributor.authorWei, X-
dc.contributor.authorLiu, N-
dc.contributor.authorJi, J-
dc.contributor.authorZhao, Lei-
dc.contributor.authorLiu, Z-
dc.contributor.authorJia, H-L-
dc.contributor.authorTang, Z-Y-
dc.contributor.authorQin, L-X-
dc.contributor.authorKloeckner, R-
dc.contributor.authorMarquardt, J-
dc.contributor.authorGreten, T-
dc.contributor.authorWang, XW-
dc.date.accessioned2020-04-03T07:23:20Z-
dc.date.available2020-04-03T07:23:20Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Biological Sciences, 2019, v. 15 n. 12, p. 2654-2663-
dc.identifier.issn1449-2288-
dc.identifier.urihttp://hdl.handle.net/10722/281897-
dc.description.abstractTransarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naïve tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE. TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p<0.0001). In addition, multivariable Cox model demonstrates that TACE Navigator was independently associated with survival (HR: 9.31, 95% CI: 3.46-25.0, p<0.001). In our validation cohorts, the association between TACE Navigator and survival remained robust in both Asian patients who received adjuvant TACE (Hong Kong: 60 months vs 25.6 months p=0.007; Shandong: 61.3 months vs 32.1 months, p=0.027) and European patients who received TACE as primary therapy (Mainz: 60 months vs 41.5 months, p=0.041). These results indicate that a TACE-specific molecular classifier is robust in predicting TACE response. This gene signature can be used to identify patients who will have the greatest survival benefit after TACE treatment and enable personalized treatment modalities for patients with HCC.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm-
dc.relation.ispartofInternational Journal of Biological Sciences-
dc.rightsInternational Journal of Biological Sciences. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectTransarterial Chemoembolization-
dc.subjecthepatocellular carcinoma-
dc.subjectprecision oncology-
dc.subjectgene signature-
dc.subjecttreatment response-
dc.titleGene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization-
dc.typeArticle-
dc.identifier.emailLee, JM-F: joyce@pathology.hku.hk-
dc.identifier.emailNg, IO-L: iolng@hku.hk-
dc.identifier.emailCheung, T-T: cheung68@HKUCC-COM.hku.hk-
dc.identifier.authorityNg, IO-L=rp00335-
dc.identifier.authorityCheung, T-T=rp02129-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/ijbs.39534-
dc.identifier.pmid31754337-
dc.identifier.pmcidPMC6854367-
dc.identifier.scopuseid_2-s2.0-85073443833-
dc.identifier.hkuros309602-
dc.identifier.volume15-
dc.identifier.issue12-
dc.identifier.spage2654-
dc.identifier.epage2663-
dc.publisher.placeAustralia-

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