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RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor.

ABSTRACT: Testicular germ cell tumors (TGCTs) are common urological neoplasms in young adult males. The outcome of TGCT depends on pathologic type and tumor stage. RNA-binding proteins (RBPs) influence numerous cancers via post-transcriptional regulation. The prognostic importance of RBPs in TGCT has not been fully investigated. In this study, we set up a prognostic risk model of TGCT using six significantly differentially expressed RBPs, namely, TRMT61A, POLR2J, DIS3L2, IFIH1, IGHMBP2, and NPM2. The expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression datasets. We observed by performing least absolute shrinkage and selection operator (LASSO) regression analyses that in the training cohort, the expression of six RBPs was correlated with disease-free survival in patients with TGCT. We assessed the specificity and sensitivity of 1-, 3-, 5-, and 10-year survival status prediction using receiver operating characteristic curve analysis and successfully validated using the test cohorts, the entire TCGA cohort, and Gene Expression Omnibus (GEO) datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses were carried out to seek the possible signaling pathways related with risk score. We also examined the association between the model based on six RBPs and different clinical characteristics. A nomogram was established for TGCT recurrence prediction. Consensus clustering analysis was carried out to identify the clusters of TGCT with different clinical outcomes. Ultimately, external validations of the six-gene risk score were performed by using the GSE3218 and GSE10783 datasets downloaded from the GEO database. In general, our study constructed a prognostic model based on six RBPs, which could serve as independent risk factor in TGCT, especially in seminoma, and might have brilliant clinical application value.

SUBMITTER: Yao L

PROVIDER: S-EPMC7990889 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor.

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