Abstract
BackgroundCumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear.MethodsMolecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature.ResultsWe identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature.ConclusionsFindings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.
Highlights
Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear
By divided samples into high-risk group and low-risk group based on whether the Riskscore is greater than 0, and analyzed the enriched pathway in both groups by using GSEA, we found that a total of 20 pathways were identified in the The Cancer Genome Atlas (TCGA) HCC cohort (Supplementary Table S6), 15 pathways were identified in the International Cancer Genome Consortium (ICGC) HCC cohort (Supplementary Table S7), and 46 pathways were identified in the GSE15654 cohort (Supplementary Table S8)
We identified the molecular subtypes of HCC based on the expression of stemness-related genes (SRGs), which provided a new molecular subtype classification of HCC, and further studied the genomic background of the molecular characteristics of HCC
Summary
Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear. Liver cancer is the fourth most lethal cancer worldwide [1]. Hepatocellular carcinoma (HCC) is rank as the major histological subtype 70–85% cases) of total liver cancer cases. Integrative studies combining transcriptome and genomic analysis have confirmed that HCC has much heterogeneous at the histo-molecular level and clinical outcomes, and the molecular diversity of HCC is tightly associated with different aetiologies and distinct mechanisms of hepato-carcinogenesis [2]. Give that only individually tailored molecular profiles and biomarkers could escape the patients from undergoing a potentially more harmful, aggressive chemical therapy or even leave them untreated, we should illustrate the natural history of HCC in individual patients by clearly understood their personal molecular characteristics. There is an increasing interest in the molecular characterization of HCC allowing prognosticate overall patient survival
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
