Role And Mechanism Of KMT5C In Malignant Progression Of Prostate Cancer

BackgroundProstate cancer(PCa)is a common malignancy of the male genitourinary system and one of the leading causes of cancer-related death in men worldwide.Diagnosis is currently made primarily by measuring prostate-specific antigen(PSA)levels and digital rectal examination,as well as prostate biopsy,and stratification is performed using the Gleason score and the International Society of Urological Pathology(ISUP)score.However,according to age,tumor stage,Gleason stage and other indicators can not effectively predict the prognosis of different patients,resulting in over-or under-treatment of these patients,so it is necessary to seek new prognostic markers to provide diagnosis and treatment basis for the treatment of patients.Lysine methyltransferase 5C(KMT5C)is a methyltransferase that specifically catalyzes the production of dimethylation(H4K20me2)and trimethylation(H4K20me3)by histone H4,thereby regulating downstream gene transcription and maintaining genome integrity.In recent years,it has been reported that KMT5 C is expressed abnormally in a variety of malignant tumors,such as pancreatic cancer,liver cancer,right-sided colon cancer,non-small cell lung cancer,bladder cancer,breast cancer,etc.,and is closely related to its occurrence and development.This suggests that KMT5 C has potential application value in the diagnosis and prognosis of these cancers,but whether it is also involved in regulating the malignant progression of prostate cancer has not yet been elucidated,so this project intends to study the expression and mechanism of KMT5 C in prostate cancer,in order to provide a theoretical basis for finding new biomarkers for prostate cancer treatment targets and prognosis.MethodsAnalysis of prostate cancer and normal prostate tissue from the Cancer Gene Atlas(TCGA)database and the Gene Expression Synthesis(GEO)database yielded differentially expressed genes(DEGs)upregulated in prostate cancer tissue,intersected them,and identified the gene KMT5 C of interest in these intersecting genes through Kaplan-Meier curves and previous research results.The expression of KMT5 C in different tumor and normal tissues was then analyzed and validated at the protein level using the Human Protein Atlas(HPA)database.Logistic regression analyzed the relationship between KMT5 C expression and clinical features of prostate cancer.The median KMT5 C m RNA expression in prostate cancer was the cut-off point,and the data were divided into KMT5 C high expression group and KMT5 C low expression group,and the overall survival(OS),disease-free survival(DFS)and biochemical recurrence-free survival(BCR-free)between the two groups were analyzed,and the effect of KMT5 C expression on the prognosis of prostate cancer could be found.Univariate COX analysis and multivariate COX analysis were used to detect the ability of KMT5 C as a prognostic factor in prostate cancer,and ROC curves and DCA curves verified the diagnostic value of KMT5 C.At the same time,combined with the relevant clinical features,the prognostic model related to KMT5 C was constructed,and the gene enrichment analysis of KEGG and GO was carried out on KMT5 C,and the correlation analysis with the invasion of prostate cancer immune cells was carried out,and finally the relevant verification was carried out at the molecular level and cell experiments.ResultThe GSE45016 and GSE104749 datasets in GEO database and TCGA database were used to find the gene KMT5 C upregulated in prostate cancer,and KMT5 C was found to be highly expressed in prostate cancer patients in paired samples.The results of logistic regression analysis showed that the high expression of KMT5 C was positively correlated with the malignant clinical features,and compared the overall survival,disease-free survival rate and biochemical recurrence-free survival rate of KMT5 C high expression group and KMT5 C low expression group,it was found that the higher the KMT5 C expression level,the worse the survival rate of patients.The results of univariate Cox analysis and multivariate Cox analysis showed that KMT5 C was an independent risk factor affecting the overall survival rate of prostate cancer patients,and ROC analysis and DCA analysis also verified the diagnostic value of KMT5 C in prostate cancer,and based on the above results,the expression level of KMT5 C was combined with clinical variables to construct a nomo nomogram prediction model.In this study,the pathways and biological functions enriched by different groups of KMT5 C were analyzed,and the immune-related analysis of KMT5 C was carried out through the TIMER database,which clarified the importance of KMT5 C in the immune system.q RT-PCR and western blotting confirmed the high expression of KMT5 C in prostate cancer cell lines at the m RNA level and protein level.Through phenotypic experiments such as KMT5 C interference,CCK-8experiment,plate cloning experiment,Transwell experiment,and cell scratch experiment,it was verified from the cellular level that high expression of KMT5 C can promote the proliferation,growth and migration of prostate cancer.DiscussionIn summary,KMT5 C is highly expressed in prostate cancer and promotes the proliferation and metastasis of prostate cancer,which may be used as a potential therapeutic target and prognostic factor for prostate cancer.