Re-Exploring Biomarkers and Therapeutic Targets in Primary Melanoma Patients: Insights from Network-Based Analysis of Microarray Data

Objective To identify novel biomarkers and therapeutic targets for primary melanoma using network-based microarray data analysis.Methods Eligible microarray datasets from the Gene Expression Omnibus(GEO)database were used to identify differentially expressed genes(DEGs).The protein-protein interaction(PPI)network,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to identify hub genes and pathways that might affect the survival of melanoma patients.Immunohistochemistry results obtained from the Human Protein Atlas(HPA)database confirmed the protein expression levels of hub genes.The Cancer Genome Atlas(TCGA)database was used to further verify the gene expression levels and conduct survival analysis.Results Three microarray datasets(GSE3189,GSE15605,and GSE46517)containing 122 melanoma and 30 normal skin tissue samples were included.A total of 262 common differentially expressed genes(cDEGs)were identified based on three statistical approaches(Fisher’s method,the random effects model(REM),and vote counting)with strict criteria.Of these,two upregulated genes,centromere protein F(CENPF)and pituitary tumortransforming gene 1(PTTG1),were selected as hub genes.HPA and TCGA database analyses confirmed that CENPF and PTTG1 were overexpressed in melanoma.Survival analysis showed that high expression levels of CENPF were significantly correlated with decreased overall survival(OS)(P=0.028).Conclusion The expression level of CENPF was significantly upregulated in melanoma and correlated with decreased OS.Thus,CENPF may represent a novel biomarker and therapeutic target for melanoma patients.

KIF2C:a novel link between Wnt/β-catenin and mTORCI signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide.HCC is refractory to many standard cancer treatments and the prognosis is often poor,highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments.Kinesin family member 2C(KIF2C)is reported to be highly expressed in several human tumors.Nevertheless,the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated.In this study,we found that KIF2C expression was significantly upregulated in HCC,and that KIF2C up-regulation was associated with a poor prognosis.Utilizing both gain and loss of function assays,we showed that KIF2C promoted HCC cell proliferation,migration,invasion,and metastasis both in vitro and in vivo.Mechanistically,we identified TBC1D7 as a binding partner of KIF2C,and this interaction disrupts the formation of the TSC complex,resulting in the enhancement of mammalian target of rapamycin complexl(mTORCI)signal transduction.Additionally,we found that KIF2C is a direct target of the Wnt/β-catenin pathway,and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORCI signaling.Thus,the results of our study establish a link between Wnt/β-catenin and mTORCI signaling,which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.

Flexible side arms of ditopic linker as effective tools to boost proton conductivity of Ni_(8)-pyrazolate metal-organic framework

Two primitive metal-organic frameworks(MOFs),Ni L1 and Ni L2,based on Ni_(8)O_(6)-cluster and ditopic pyrazolate linkers,L1(with rigid alkyne arms)and L2(with flexible alkyne chains),were prepared.The proton conductivities of these MOFs in pristine form and imidazole-encapsulated forms,Im@Ni L1 and Im@Ni L2,were measured and compared.Upon introduction of imidazole molecules,the proton conductivity could be increased by 3 to 5 orders of magnitude and reached as high as 1.72×10^(-2)S/cm(at 98%RH and 80℃).Also,whether imidazole molecules were introduced or not,Ni_(8)O_(6)-based MOFs with L2 in general gave better proton conductivity than those with L1 signifying that flexible side arms indeed assist proton conduction probably via establishment of efficient proton-conducting channels along with formation of highly ordered domains of water/imidazole molecules within the network cavities.Beyond the active Ni_(8)O_(6)-cluster,tuning flexibility of linker pendants serves as an alternative approach to regulate/modulate the proton conductivity of MOFs.