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A novel tp53-associated nomogram to predict the overall survival in patients with pancreatic cancer

Authors :
Xun Liu
Bobo Chen
Jiahui Chen
Shaolong Sun
Source :
BMC Cancer, Vol 21, Iss 1, Pp 1-15 (2021)
Publication Year :
2021
Publisher :
BMC, 2021.

Abstract

Abstract Background Gene mutations play critical roles in tumorigenesis and cancer development. Our study aimed to screen survival-related mutations and explore a novel gene signature to predict the overall survival in pancreatic cancer. Methods Somatic mutation data from three cohorts were used to identify the common survival-related gene mutation with Kaplan-Meier curves. RNA-sequencing data were used to explore the signature for survival prediction. First, Weighted Gene Co-expression Network Analysis was conducted to identify candidate genes. Then, the ICGC-PACA-CA cohort was applied as the training set and the TCGA-PAAD cohort was used as the external validation set. A TP53-associated signature calculating the risk score of every patient was developed with univariate Cox, least absolute shrinkage and selection operator, and stepwise regression analysis. Kaplan-Meier and receiver operating characteristic curves were plotted to verify the accuracy. The independence of the signature was confirmed by the multivariate Cox regression analysis. Finally, a prognostic nomogram including 359 patients was constructed based on the combined expression data and the risk scores. Results TP53 mutation was screened to be the robust and survival-related mutation type, and was associated with immune cell infiltration. Two thousand, four hundred fifty-five genes included in the six modules generated in the WGCNA were screened as candidate survival related TP53-associated genes. A seven-gene signature was constructed: Risk score = (0.1254 × ERRFI1) - (0.1365 × IL6R) - (0.4400 × PPP1R10) - (0.3397 × PTOV1-AS2) + (0.1544 × SCEL) - (0.4412 × SSX2IP) – (0.2231 × TXNL4A). Area Under Curves of 1-, 3-, and 5-year ROC curves were 0.731, 0.808, and 0.873 in the training set and 0.703, 0.677, and 0.737 in the validation set. A prognostic nomogram including 359 patients was constructed and well-calibrated, with the Area Under Curves of 1-, 3-, and 5-year ROC curves as 0.713, 0.753, and 0.823. Conclusions The TP53-associated signature exhibited good prognostic efficacy in predicting the overall survival of PC patients.

Details

Language :
English
ISSN :
14712407
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.633449092c84bfdb242602ed512c5e7
Document Type :
article
Full Text :
https://doi.org/10.1186/s12885-021-08066-2