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Article: Development of an oncogenic dedifferentiation SOX signature with prognostic significance in hepatocellular carcinoma

TitleDevelopment of an oncogenic dedifferentiation SOX signature with prognostic significance in hepatocellular carcinoma
Authors
KeywordsOncogenic dedifferentiation
Prognostic value
Stem cell-like properties
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/
Citation
BMC Cancer, 2019, v. 19 n. 1, p. article no. 851 How to Cite?
AbstractBackground: Gradual loss of terminal differentiation markers and gain of stem cell-like properties is a major hall mark of cancer malignant progression. The stem cell pluripotent transcriptional factor SOX family play critical roles in governing tumor plasticity and lineage specification. This study aims to establish a novel SOX signature to monitor the extent of tumor dedifferentiation and predict prognostic significance in hepatocellular carcinoma (HCC). Methods: The RNA-seq data from The Cancer Genome Atlas (TCGA) LIHC project were chronologically divided into the training (n = 188) and testing cohort (n = 189). LIRI-JP project from International Cancer Genome Consortium (ICGC) data portal was used as an independent validation cohort (n = 232). Kaplan-Meier and multivariable Cox analyses were used to examine the clinical significance and prognostic value of the signature genes. Results: The SOX gene family members were found to be aberrantly expressed in clinical HCC patients. A five-gene SOX signature with prognostic value was established in the training cohort. The SOX signature genes were found to be closely associated with tumor grade and tumor stage. Liver cancer dedifferentiation markers (AFP, CD133, EPCAM, and KRT19) were found to be progressively increased while hepatocyte terminal differentiation markers (ALB, G6PC, CYP3A4, and HNF4A) were progressively decreased from HCC patients with low SOX signature scores to patients with high SOX signature scores. Kaplan-Meier survival analysis further indicated that the newly established SOX signature could robustly predict patient overall survival in both training, testing, and independent validation cohort. Conclusions: An oncogenic dedifferentiation SOX signature presents a great potential in predicting prognostic significance in HCC, and might provide novel biomarkers for precision oncology further in the clinic.
Persistent Identifierhttp://hdl.handle.net/10722/278130
ISSN
2018 Impact Factor: 2.933
2015 SCImago Journal Rankings: 1.627
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, MM-
dc.contributor.authorTang, YQ-
dc.contributor.authorGong, YF-
dc.contributor.authorCheng, W-
dc.contributor.authorLi, H-L-
dc.contributor.authorKong, F-E-
dc.contributor.authorZhu, W-J-
dc.contributor.authorLiu, S-S-
dc.contributor.authorHuang, L-
dc.contributor.authorGuan, X-Y-
dc.contributor.authorMa, N-F-
dc.contributor.authorLiu, M-
dc.date.accessioned2019-10-04T08:08:04Z-
dc.date.available2019-10-04T08:08:04Z-
dc.date.issued2019-
dc.identifier.citationBMC Cancer, 2019, v. 19 n. 1, p. article no. 851-
dc.identifier.issn1471-2407-
dc.identifier.urihttp://hdl.handle.net/10722/278130-
dc.description.abstractBackground: Gradual loss of terminal differentiation markers and gain of stem cell-like properties is a major hall mark of cancer malignant progression. The stem cell pluripotent transcriptional factor SOX family play critical roles in governing tumor plasticity and lineage specification. This study aims to establish a novel SOX signature to monitor the extent of tumor dedifferentiation and predict prognostic significance in hepatocellular carcinoma (HCC). Methods: The RNA-seq data from The Cancer Genome Atlas (TCGA) LIHC project were chronologically divided into the training (n = 188) and testing cohort (n = 189). LIRI-JP project from International Cancer Genome Consortium (ICGC) data portal was used as an independent validation cohort (n = 232). Kaplan-Meier and multivariable Cox analyses were used to examine the clinical significance and prognostic value of the signature genes. Results: The SOX gene family members were found to be aberrantly expressed in clinical HCC patients. A five-gene SOX signature with prognostic value was established in the training cohort. The SOX signature genes were found to be closely associated with tumor grade and tumor stage. Liver cancer dedifferentiation markers (AFP, CD133, EPCAM, and KRT19) were found to be progressively increased while hepatocyte terminal differentiation markers (ALB, G6PC, CYP3A4, and HNF4A) were progressively decreased from HCC patients with low SOX signature scores to patients with high SOX signature scores. Kaplan-Meier survival analysis further indicated that the newly established SOX signature could robustly predict patient overall survival in both training, testing, and independent validation cohort. Conclusions: An oncogenic dedifferentiation SOX signature presents a great potential in predicting prognostic significance in HCC, and might provide novel biomarkers for precision oncology further in the clinic.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/-
dc.relation.ispartofBMC Cancer-
dc.rightsBMC Cancer. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectOncogenic dedifferentiation-
dc.subjectPrognostic value-
dc.subjectStem cell-like properties-
dc.titleDevelopment of an oncogenic dedifferentiation SOX signature with prognostic significance in hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailGuan, X-Y: xyguan@hku.hk-
dc.identifier.authorityGuan, X-Y=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12885-019-6041-2-
dc.identifier.pmid31462277-
dc.identifier.pmcidPMC6714407-
dc.identifier.scopuseid_2-s2.0-85071619942-
dc.identifier.hkuros306354-
dc.identifier.volume19-
dc.identifier.issue1-
dc.identifier.spagearticle no. 851-
dc.identifier.epagearticle no. 851-
dc.publisher.placeUnited Kingdom-

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