Screening Of Biomarkers For Prognosis Of Metastatic Uveal Melanoma

Objective: Metastatic uveal melanoma(uveal melanoma,UM)has the disadvantages of high-grade malignancy,poor prognosis and limited therapy method.Prognostic evaluation in patients with metastatic uveal melanoma is critical.Exploring molecular markers of prognosis is helpful for accurate diagnosis classification,risk stratification and prognosis evaluation clinically.The rapid development of high-throughput sequencing technology,massive genome and other complete data provide a good opportunity to investigate the genesis,development,metastasis and prognosis of tumors.In this study,resources from public databases were mined using bioinformatics methods to screen prognostic biomarkers for metastatic uveal melanoma.Methods: The uveal melanoma-associated m RNA expression profile chip data and clinical survival prognosis data were downloaded from the gene expression omnibus(GEO)and the cancer genome atlas(TCGA).The original gene chip data in GEO database dataset GSE22138 and GSE27831 were pretreated with the “affy”package in R language,and the genes differentially expressed(DEGs)in non-metastatic uveal melanoma and metastatic uveal melanoma samples were screened by “limma” package.The protein-protein interaction network(PPI)was constructed by STRING database,and hub genes were obtained by screening cyto Hubba plug-ins in the Cytoscape.Kaplan-Meier survival curve was used to evaluate the overall survival rate of patients with high and low gene expression.The correlation of screened DEGs with the prognosis was analyzed with LASSO regression model,and ROC curve was used to evaluate the diagnostic value of prognostic markers.Results: The results showed that 837 DEGs were obtained by analyzing the microarray data of GSE22138 and GSE27831.Ten Hub genes such as CXCL9,POMC,GNGT1,S1PR1,P2RY14,C5AR1,ANXA1,CXCR1,AGT and NPB were analyzed from PPI network.By LASSO-Cox regression model,WNT10B(P<0.001)、PCDHA10(P<0.001)、CFAP65(P<0.001)、KRTCAP2(P<0.001)、ACOT12(P<0.001)、PITX2(P=0.001)、GRAP2(P<0.001),and IGHMBP2(P<0.001)were found to be closely related to the prognosis of patients.Kaplan Meier curve showed that high expression of ACOT12(HR=0.05,95%CI: 0.02～0.12,P<0.001)、CFAP65(HR=0.18,95%CI: 0.08～0.42,P<0.001)、IGHMBP2(HR=0.08,95%CI: 0.03～0.18,P<0.001),and PCDHA10(HR=0.09,95%CI: 0.04～0.2,P<0.001)were related to poor prognosis,while high expression of GRAP2(HR=16.85,95%CI: 7.39～38.43,P<0.001)、KRTCAP2(HR=9.8,95%CI: 3.9～24.63,P<0.001)、PITX2(HR=4.38,95%CI: 1.93～9.93,P=0.002),and WNT10B(HR=13.41,95%CI: 5.63～31.95,P<0.001)suggested better prognosis.ROC curve showed that KRTCAP2(AUC=0.79)、 PCDHA10(AUC=0.795)和 WNT10B(AUC=0.769)、 ACOT12(AUC=0.71),and CFAP65(AUC=0.709)had good diagnostic value in metastatic uveal melanoma.Conclusion: This study analyzed and identified 10 key genes,such as CXCL9,POMC,GNGT1 and S1PR1,that may be involved in the metastatic process of uveal melanoma by mining the information of patients with metastatic uveal melanoma in a public database and using bioinformatics and screened KRTCAP2、PCDHA10、WNT10B、ACOT12,and CFAP65 biomarkers strongly associated with patient prognosis.This study provides a new idea for further research on the mechanism of metastatic uveal melanoma,and provides a reference for study of large-scale metastatic uveal melanoma genomics.