Prognostic Value Of Dynactin Gene Family Expression In Skin Cutaneous Melanoma

Objective Skin cutaneous melanoma(SKCM)is a cancer caused by the malignant transformation of melanocytes from the basal layer of the skin.It is one of the most dangerous types of skin cancer in the world.Factors such as ultraviolet light(UV)and malignant transformation of moles are high risk factors for melanoma.At present,most of the treatment methods for SKCM are surgical resection,radiotherapy and chemotherapy.According to statistics in the United States,the 5-year survival rate of SKCM patients after treatment is about 98%,and the 5-year survival rate of patients with stage IV is only 3%.However,there is no gold standard biomarker for predicting the prognosis of SKCM,and how to predict the survival rate of SKCM patients has important guiding significance for the clinical individualized and precise treatment of SKCM patients.Dynactin(DCTN)is a multi-subunit protein of 6 subunits encoded by the DCTN gene family,including DCTN1,DCTN2,DCTN3,DCTN4,DCTN5,and DCTN6.After literature searching,we found that in previous studies,the DCTN gene family played different roles in different diseases,especially their level of expression played different roles in differenttumors.Methods Therefore,we investigated the prognostic value of the expression level of the DCTN gene family in SKCM.Gene expression profile data including gene expression level,survival days,survival status,gender,age,and tumor stage were all derived from the TCGA database(The Cancer Genome Atlas,TCGA).The database contains detailed clinical information and prognostic data for 472 patients with SKCM.In this study,Kaplan-Meier survival analysis and Cox regression model(proportional risk model)were used to perform single factor survival analysis and multivariate survival analysis of DCTN gene family and calculate Hazard ratio(HR)and 95% CI(confidence interval).Predicting the DCTN gene family through enrichment tools such as DAVID(The Database for Annotation,Visualization,and Integrated Discovery),GeneMANIA,protein-protein interaction network(PPI network),and GSEA(gene set enrichment analysis).The biological function as well as the prospective molecular mechanism.Results We found that in 458 patients with SKCM,the patients with low expression of DCTN2 and DCTN5,the high expression of DCTN6 had better overall survival(OS)(P<0.05);the results about remaining genes in the DCTN gene family in survival analysis had no statistically significant;there was no significant difference in the expression of those three genes in each tumor stage.In the nomogram model,the score for tumor stage was increased by the advanced tumor stage;the high expression of DCTN2,DCTN5 and the low expression of DCTN6 had higher score;the higher the total score,the lower the survival rate of SKCM patients.Survival of SKCM patients can be visually predicted by the nomogram.Enrichment results showed that DCTN2,DCTN5 and DCTN6 were involved in UV response,cell cycle,apoptosis,WNT cell signaling pathway and P53 cell signaling pathway.Conclusion Through this research,we found that patients with low expression of DCTN2 and DCTN5 and high expression of DCTN6 in SKCM had higher overall survival rates,established a nomogram for predictive the survival rate of SKCM patients.The,DCTN2,DCTN5 and DCTN6 can be used as potential biomarkers for predicting the prognosis of SKCM patients,provides new guidance for prognosis prediction,individualized treatment,and further research about SKCM.