A novel nine gene signature integrates stemness characteristics associated with prognosis in hepatocellular carcinoma

Cancer stem cells(CSCs)are heterogeneous with self-renewal and differentiation ability.The mRNA expression-based stemness index(mRNAsi)described the similarity between tumor cells and CSCs,which is positively associated with the poor prognosis of cancer patients.However,the key prognostic genes related to mRNAsi in hepatocellular carcinoma(HCC)remains unclear.A 9-gene signature related to mRNAsi and HCC prognosis including PSMG3,SNRPD1,DTYMK,PIGU,NME1,TXNL4A,IPO4,PES1,and REXO4 was obtained.High expression of this signature indicates poor prognosis of HCC.PIGU was an independent prognostic factor of HCC,which was significantly associated with progression of HCC.Among them,DTYMK and NME1 enriched in pyrimidine metabolism,SNRPD1 and TXNL4A enriched in spliceosome and PIGU enriched in glycosyl phosphatidylinositol(GPI)-anchor biosynthesis pathways.High levels of IPO4,NME1,PES1,PIGU and SNRPD1 were closely associated with metastasis of HCC,and low levels of IPO4,PIGU and REOX4 were significantly associated with sorafenib resistance of HCC.High expression of the 9-gene signature was negatively correlated with the stromal cell infiltration,and positively correlated with specific immune subtypes-related to angiogenesis,M1/M2 macrophage polarization,and M2 response.The 9-gene signature was negatively correlated with the stroma,and SNRPD1 and TXNL4 were positively correlated with immune infiltrate.NME1 was negatively correlated with tumor purity.Therefore,a 9-gene signature related to mRNAsi and poor prognosis in HCC were identified,which can be used as biomarkers for the diagnosis of HCC and functional mechanism exploration of CSCs in HCC.These genes such as IPO4 and PIGU might drive the transition of tumor cells into CSCs which possibly controls the balance between metastasis and drug resistance in HCC.The challenge on balance between metastasis and drug resistance for tumor therapy was firstly reported by the present study.

Identification of key genes controlling cancer stem cell characteristics in gastric cancer

BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cell-related genes in GC.METHODS RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database,and the results of the GC mRNA expression-based stemness index(mRNAsi)were analyzed.Weighted gene coexpression network analysis was then used to find modules of interest and their key genes.Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter,and the online database Oncomine was used to assess the expression of key genes in GC.RESULTS mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues(P<0.0001).A total of 16 modules were obtained from the gene coexpression network;the brown module was most positively correlated with mRNAsi.Sixteen key genes(BUB1,BUB1 B,NCAPH,KIF14,RACGAP1,RAD54 L,TPX2,KIF15,KIF18 B,CENPF,TTK,KIF4 A,SGOL2,PLK4,XRCC2,a n d C1 orf112)were identified in the brown module.The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component,the sister chromatid segregation biological process,the motor activity molecular function,and the cell cycle and homologous recombination pathways.Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes(RAD54 L,TPX2,and XRCC2)were consistently related.CONCLUSION Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.RAD54 L,TPX2,and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.