Abstract
BACKGROUND: Testicular cancer is a very common malignancy in young men. Although testicular cancer has a high cure rate, patients have a high long-term risk of secondary malignant tumors and cardiovascular disease. In addition, for patients resistant to traditional treatment methods, new treatment methods and methods for predicting prognosis are also urgently needed. METHODS: Gene expression profiles of 165 normal testicular tissues and 156 testicular germ cell tumor (TGCT) tissues from GTEx database and TCGA database were used to obtain differentially expressed genes (DEGs) in TGCT. Through the ImmPort database, we obtained immune-related genes (IRGs). Univariate Cox regression analysis was used to identify prognostic IRGs. A transcription factor regulatory network was constructed to clarify the possible regulatory mechanism for the differential expression of these IRGs. Multivariate Cox regression analysis was used to establish a prognostic model. Gene expression data and related survival data of 108 TCGT patients from GEO database were used for external validation. Survival analysis, receiver operating characteristic curves (ROC) curve analysis, independent prognostic analysis, principal component analysis (PCA) and clinical correlation analysis were performed to evaluate this model. RESULTS: Three hundred and thirty-three IRGs were differentially expressed between TGCT and normal testicular tissues. We established a prognostic model (riskScore) based on 5 risk genes (SEMA6B, SEMA3G, OBP2B, INSL6 and RETN). Whether in the training cohort, the testing cohort or the entire TCGA cohort, this model could accurately stratify patients with different survival outcomes. The prognostic value of riskScore and 5 risk genes was also confirmed in the GEO database. GSEA analysis showed that DEGs in patients with better prognosis were enriched in immune-related pathways, while DEGs in patients with poorer prognosis were enriched in cancer-related pathways and cardiovascular disease-related pathways. Finally, a new Nomogram with higher prognostic value was constructed to better predict the 1-year PFS, 3-year PFS and 5-year PFS of TCGT patients. CONCLUSIONS: We successfully established an immune-related risk model with high prognostic value and created a new Nomogram. We found that different immune status in tumor microenvironment may be responsible for the different survival outcomes among TGCT patients.