Analysis And Prediction Of Potential Therapeutic Targets For NK/T Cell Lymphoma Based On Bioinformatics

Objectives:Bioinformatics technology was used to process the sequencing data of NK/T cell lymphoma(NKTCL)from GEO database to screen out differentially expressed genes and explore the signal pathways that may be affected.The relationship between the expression of target genes and clinicopathological features of patients was utilized to evaluate the clinical value of screening genes as therapeutic targets.Cell models of radiotherapy and chemotherapy in vitro were constructed to explore the effects of cyclin D1(CCND1)on tumor growth,providing a basis for further study of NKTCL treatment strategies.Methods:NKTCL sequencing data from GEO database GSE19067 and GSE80632 were collected."AFFy" package and "SVA" package in R software were used to preprocess the data."Limma" package was used to screen different expression genes(DEGs).GO and KEGG functional enrichment analysis was performed on DEGs.The protein interaction network was constructed by STRING database and visualized through Cytoscape software.(1)Tumor tissue samples from 60 patients with confirmed NKTCL in a hospital were collected.Morphological changes of tumor tissues were observed by hematoxylin-eosin staining(HE).Immunohistochemical staining(IHC)was used to detect the expression of CCND1 in NKTCL tumor tissues.SPSS software was used to analyze the relationship between CCND1 expression and clinical characteristics of patients.(2)The growth of NKTCL tumor cells was detected by CCK-8 kit.q PCR was used to measure the expression of CCND1 in NKTCL tumor cells.Results:(1)Two NKTCL datasets were analyzed after screening.Compared with the normal group,there were 3425 DEGs in the NKTCL samples,among which 1793 genes were expressed higher,and 1632 genes were expressed lower.(2)By GO and KEGG analysis,cell cycle-related gene expression and signal pathway were significantly different from normal group(P<0.05).CCND1 gene was significantly overexpressed in NKTCL tumor samples(P<0.05).CCND1 was selected as the target to be verified.(3)IHC showed that levels of CCND1 expression were positively expressed in NKTCL.Upregulation of CCND1 was closely correlated with the patient’s age ≥60 years,the influence of the lesion on bone marrow,the distant metastasis of the lesion,the onset of B symptom,abnormal levels of β2-MG in peripheral blood,advanced stage of diagnosis and poor initial treatment effect(P<0.05).There was no correlation with gender,whether the primary site was nasal cavity,the level of Ki-67 in pathological indexes,EBER,TIA-1,Granzyme B expression and LDH level in peripheral blood(P>0.05).(4)Tumor cell growth was significantly reduced after X-ray irradiation(and CCND1 inhibitor,.(5)CCND1 was highly expressed in NKTCL tumor cells.CCND1 expression was decreased in NKTCL tumor cells after irradiation and CCND1 inhibitor.Conclusions:(1)The potential therapeutic targets of NK/T cell lymphoma can be effectively predicted by using large database combined with bioinformatics.(2)CCND1 gene expression was significantly increased in NK/T cell lymphoma,which was significantly correlated with clinical characteristics of patients.(3)Inhibition of CCND1 and/or radiation can effectively inhibit the growth of NKTCL cells.CCND1 can be considered as a therapeutic target for NK/T cell lymphoma.