Bioinformatics analysis of key biomarkers for cryptorchidism and potential risk of carcinogenesis

Abstract Background Cryptorchidism is characterized by undescended or incomplete descent of the testes. The pathogenesis of cryptorchidism has not been fully elucidated. In addition, patients with cryptorchidism are at a higher risk of malignancy than normal individuals, and its etiology and underlying molecular mechanisms need to be further investigated. Methods Datasets GSE16191 and GSE25518 were downloaded from the Gene Expression Omnibus database to identify the common differentially expressed genes (DEGs). Gene enrichment analyses were performed using the WebGestalt database. A protein-protein interaction network of DEGs was constructed using the STRING database, of which hub genes were identified by Cytoscape software. The GEPIA database was used to validate the expression of the hub genes of cryptorchidism in testicular cancer, and then the protein level of genes was detected in the HPA database. The analysis of immune cell infiltration was conducted in the R package. The clinical significance of the selected genes was analyzed from four aspects: clinical correlation, overall survival (OS), recurrence-free survival (RFS), and receiver operating characteristic (ROC) curve. Results Of the 438 common DEGs identified, 134 were up-regulated and 304 were down-regulated. Biological functions analysis identified important signaling pathways, key functional modules, and co-expression networks in cryptorchidism. Nine hub genes (HNRNPM, SF1, U2SURP, SNRPA1, AQR, RBM39, PCBP2, RBM5, and HNRNPU) were identified in cryptorchidism, four (SF1, HNRNPM, RBM5, and AQR) of which were significantly expressed in testicular cancer. The high expression of the genes SF1 and HNRNPM predicted poor RFS in cancer patients. Moreover, genes AQR and HNRNPM may contribute to malignant transformation from cryptorchidism to cancer via the spliceosome pathway. Conclusion Our study revealed the potential molecular mechanisms under the pathogenesis of cryptorchidism and its carcinogenesis. The biomarkers identified in this study may provide a theoretical basis and new ideas for further mechanism research of cryptorchidism.