Alternative splicing(AS)in the tumor biological process has provided a novel perspective on carcinogenesis.However,the clinical significance of individual AS patterns of adrenocortical carcinoma(ACC)has been underesti...Alternative splicing(AS)in the tumor biological process has provided a novel perspective on carcinogenesis.However,the clinical significance of individual AS patterns of adrenocortical carcinoma(ACC)has been underestimated,and in-depth investigations are lacking.We selected 76 ACC samples from the Cancer Genome Atlas(TCGA)SpliceSeq and SpliceAid2 databases,and 39 ACC samples from Fudan University Shanghai Cancer Center(FUSCC).Prognosis-related AS events(PASEs)and survival analysis were evaluated based on prediction models constructed by machine-learning algorithm.In total,23,984 AS events and 3,614 PASEs were detected in the patients with ACC.The predicted risk score of each patient suggested that eight PASEs groups were significantly correlated with the clinical outcomes of these patients(p<0.001).Prognostic models produced AUC values of 0.907 in all PASEs’groups.Eight splicing factors(SFs),including BAG2,CXorf56,DExD-Box Helicase 21(DDX21),HSPB1,MBNL3,MSI1,RBMXL2,and SEC31B,were identified in regulatory networks of ACC.DDX21 was identified and validated as a novel clinical promoter and therapeutic target in 115 patients with ACC from TCGA and FUSCC cohorts.In conclusion,the strict standards used in this study ensured the systematic discovery of profiles of AS events using genome-wide cohorts.Our findings contribute to a comprehensive understanding of the landscape and underlying mechanism of AS,providing valuable insights into the potential usages of DDX21 for predict-ing prognosis for patients with ACC.展开更多
基金supported by National Key Research and Development Program of China(No.2019YFC1316000)Fuqing Scholar Student Scientific Research Program of Shanghai Medical College,Fudan University(No.FQXZ202112B)+1 种基金Natural Science Foundation of Shanghai(No.20ZR1413100)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Alternative splicing(AS)in the tumor biological process has provided a novel perspective on carcinogenesis.However,the clinical significance of individual AS patterns of adrenocortical carcinoma(ACC)has been underestimated,and in-depth investigations are lacking.We selected 76 ACC samples from the Cancer Genome Atlas(TCGA)SpliceSeq and SpliceAid2 databases,and 39 ACC samples from Fudan University Shanghai Cancer Center(FUSCC).Prognosis-related AS events(PASEs)and survival analysis were evaluated based on prediction models constructed by machine-learning algorithm.In total,23,984 AS events and 3,614 PASEs were detected in the patients with ACC.The predicted risk score of each patient suggested that eight PASEs groups were significantly correlated with the clinical outcomes of these patients(p<0.001).Prognostic models produced AUC values of 0.907 in all PASEs’groups.Eight splicing factors(SFs),including BAG2,CXorf56,DExD-Box Helicase 21(DDX21),HSPB1,MBNL3,MSI1,RBMXL2,and SEC31B,were identified in regulatory networks of ACC.DDX21 was identified and validated as a novel clinical promoter and therapeutic target in 115 patients with ACC from TCGA and FUSCC cohorts.In conclusion,the strict standards used in this study ensured the systematic discovery of profiles of AS events using genome-wide cohorts.Our findings contribute to a comprehensive understanding of the landscape and underlying mechanism of AS,providing valuable insights into the potential usages of DDX21 for predict-ing prognosis for patients with ACC.
