Open AccessCharacterization of progression-related alternative splicing events in testicular germ cell tumors
Author(s) -
Chuanjie Zhang,
Zongtai Li,
Kan-Jie Shen,
Lu Chen,
Danfeng Xu,
Yi Gao
Publication year - 2021
Publication title -
asian journal of andrology/asian journal of andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 74
eISSN - 1745-7262
pISSN - 1008-682X
DOI - 10.4103/aja.aja_30_20
Subject(s) - univariate , oncology , alternative splicing , proportional hazards model , univariate analysis , pathological , receiver operating characteristic , biology , tumor progression , rna splicing , medicine , survival analysis , multivariate analysis , stage (stratigraphy) , testicular germ cell tumor , cancer , multivariate statistics , testicular cancer , gene , genetics , rna , messenger rna , paleontology , statistics , mathematics
Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan-Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10 -7 ). We also analyzed the biological functions of the PFS-related AS-related genes and found enrichment in pathways associated with DNA repair and modification. Finally, we identified a regulatory network of splicing factors with expression levels that correlated significantly with AS events in TGCT. Collectively, this study identifies a novel method for risk stratification of patients and provides insight into the molecular events underlying TGCT.