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.
Highlights
Testicular germ cell tumors (TGCTs) are the most common malignant neoplasms in young adult males between 20 and 40 years old despite being regarded as rare tumor types that account for only 1% of solid neoplasms in men (Tsili et al, 2019)
The expression data and clinical information of RNAbinding proteins (RBPs) in 156 patients with TGCT were downloaded from The Cancer Genome Atlas (TCGA) datasets,1 and the data of 165 healthy controls were obtained from Genotype-Tissue Expression (GTEx)
The results presented as forest maps obviously indicate that the risk score correlated independently with disease-free survival (DFS) in univariate [hazard ratio (HR) = 1.155, confidence interval (CI) = 1.086−1.228, ∗∗∗p < 0.001], and multivariate Cox regression analyses (HR = 1.226, 95% CI = 1.132−1.327, ∗∗∗p < 0.001; Figures 8A,B)
Summary
Testicular germ cell tumors (TGCTs) are the most common malignant neoplasms in young adult males between 20 and 40 years old despite being regarded as rare tumor types that account for only 1% of solid neoplasms in men (Tsili et al, 2019). TGCT mortality is lower than 10% and the cure rate has reached 95% because of the application of cisplatin-based chemotherapy (Diamantopoulos and Kortsaris, 2010; Cheng et al, 2018), 10–15% of the patients are refractory to firstline chemotherapy and TGCT has poor outcome (Oechsle et al, 2011). Serum tumor markers, such as alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactose dehydrogenase (LDH), are widely applied clinically and effective in the diagnosis, staging, risk stratification, treatment, and evaluation of patients’ response to chemotherapy in TGCT (Marshall et al, 2019). A risk model for TGCT prognosis prediction has not been designed so far
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