Characterization of progression-related alternative splicing events in testicular germ cell tumors

• 作者: Chuan-Jie Zhang Zong-Tai Li Kan-Jie Shen Lu Chen Dan-Feng Xu Yi Gao
• 来源期刊: 亚洲男性学杂志（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ORIGINAL ARTICLE
• 页码范围: 259-265
• 页数: 7页
• 语种: 英文
• DOI: 10.4103/aja.aja_30_20

摘要

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.