Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors

Abstract

Background: Testicular germ cell tumors (TGCTs) are commonly diagnosed tumors in young men. However, a satisfactory approach to predict relapse of stage I TGCTs is still lacking. Therefore, this study aimed to develop a robust risk score model for stage I TGCTs. Method: RNA-sequence data of stage I TGCTs and normal testis samples were downloaded and analyzed to identify different expression genes. Gene-based prognostic model was constructed in The Cancer Genome Atlas (TCGA) using least absolute shrinkage and selection operator (LASSO) regression analysis and validated in GSE99420 dataset. Potential biological functions of the genes in prognostic model were determined via Gene Set Enrichment Analysis (GSEA) between high-risk and low-risk patients. Results: A total of 9,391 differentially expressed genes and 84 prognosis-related genes were identified. An eight-gene-based risk score model was constructed to divide patients into high or low risk of relapse. The low-risk patients had a significantly better relapse-free survival (RFS) than high-risk patients in both training and validation cohorts (HR = 0.129, 95% CI = 0.059-0.284, P < 0.001; HR = 0.277, 95% CI = 0.116-0.661, P = 0.004, respectively). The area under the receiver operating characteristic curve (AUC) values at 5 years was 0.805 and 0.724 in the training and validation cohorts, respectively. Functional enrichment analyses showed that DNA replication, ribosome, cell cycle, and TGF-beta signaling pathway may contribute to the relapse process. Conclusion: In summary, our analysis provided a novel eight-gene signature that could predict RFS in stage I TGCT patients.

Evaluation of gene expression of PLEKHS1, AADAC, and CDKN3 as novel genomic markers in gastric carcinoma

“…Coinciding with the present findings Zhou et al [ 22 ] by using the TCGA database, showed that PLEKHS1 was downregulated in stage I Testicular germ cell tumors (TGCTs) patients, and it was reported as one of the new eight-gene signatures that could be used in the prediction of relapse-free survival (RFS) having a protective role in TGCT relapse.…”

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

“…However, normal tissue information is not available for all types of cancer, which constitutes a limitation in some studies that include TGCTs. This limitation can be overcome by the additional use of other public databases, like the Genotype-Tissue Expression (GTEx) database, which contains normal testis expression data that enable the necessary comparisons [46]. Still, the number of TGCT patients is relatively low, even in the TCGA database, with a current number of 263 cases, of which 150 cases provide DNA methylation data [42].…”

“…Previously, an eight-gene panel was generated for stratifying patients with stage I TGCTs into low and high risk of relapse, but the study only included gene expression, with data corroborated between TCGA and GTEx [46]. The genes (GPR174, TCTEX1D1, TMEM89, CST2, SRARP, GSC, PEKHS1, FLG2) included in the risk score model may be further investigated to detect methylation status or mutations in order to further our understanding and support their use [46].…”

The Critical Gene Screening to Prevent Chromophobe Cell Renal Carcinoma Metastasis through TCGA and WGCNA

“…There is currently no more comprehensive tumor gene expression profile database than the Cancer Genome Atlas (TCGA), which is distinguished by its large sample size and rich clinical information [ 13 ]. An analysis of gene-phenotype relationships called Weighted Gene Coexpression Network Analysis (WGCNA) has gained popularity for its ability to investigate complex relationships between genes and phenotypes.…”