Cyclin-dependent Kinases 7(CDK7) Expression In Human Hepatocellular Carcinoma:Association With HCC Progression,Prognosis And Cell Proliferative Capacity

Background:Hepatocellular carcinoma（HCC）is one of the most common malignancy cancers in the world,and contribute a high cancer mortality globally.The multistep progression of HCC is highly related to the activation of oncogene and deactivation of cancer suppressor gene.Cyclin-dependent kinase 7（CDK7）gene is responsible to maintain normal cell cycle as a gatekeeper,and also plays an important part in RNA transcription.Although previous studies demonstrate CDK7 is highly expressed in multiple cancers and associated to the progression and prognosis of these cancers,the potential role of CDK7 played in HCC is still needed to explore.Methods:Data consisting of the CDK7 expression levels,patient phenotypes（including age、gender、histologic grade、TNM stage）and their matched survival were acquired from The Cancer Genome Atlas（TCGA）database.The association of CDK7expression level with clinicopathological factors and cell proliferation level was analyzed.The HCC transcriptome data in the GEO database was inquired and analyzed using GEO2R.Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when the expression of CDK7 was inhibited by either shCDK7 or THZ1.Results:Based on the transcriptome and survival data in TCGA database,the CDK7 expression level was inversely proportional to the overall survival of HCC patients（pooled HR=1.51,95%CI=1.06-2.15）.For further investigation,the clinical features of HCC were integrated with the expression level of CDK7.A high expression of CDK7 was proportional to the survival time of HCC patients(P=2.38×10^-3),the neoplasm histologic grade(P<1×10^-4)and cell proliferation(P<1×10^-3).Moreover,CDK7 expression in the liver tumor was higher than that in non-tumor tissues(T-test=6.04,P=2.27×10^-8).For HCC patients,CDK7expression was higher in tumor tissues than in the para-carcinoma tissues,based on five GEO datasets(Z score=-6.20,P=5.64×10^-10).In SMMC-7721 and Huh7 cell lines,CDK7 shRNA-transfected cells showed significantly lower capabilities of cell growth and proliferation than those of the shRNA control group after 48 hours of cell culture.Furthermore,the cell proliferation capacity was also inhibited when SMMC-7721 cells(P=6.47×10^-4)or Huh7 cells(P=2.52×10^-2)were exposed to THZ1.Conclusions:The CDK7 expression level in HCC is associated with HCC progression,prognosis and cell proliferation capacity.CDK7 may act as a potential target for HCC,and THZ1 might be a potent medicine for HCC treatment.