A cellular senescence-related genes model allows for prognosis and treatment stratification of cervical cancer: a bioinformatics analysis and external verification

Abstract

Background: Cervical cancer (CC) is highly lethal and aggressive with an increasing trend of mortality for females. Molecular characterization-based methods hold great promise for improving the diagnostic accuracy and for predicting treatment response. Methods: The mRNAs expression data of CC patients and cellular senescence-related genes were obtained from the Cancer Genome Atlas (TCGA) and CellAge databases, respectively. Differentially expressed genes (DEGs) of senescence related genes between tumor and normal tissues were used for Least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model. Univariate and LASSO regression analyses were applied to establish a predictive nomogram. The performance of the nomogram were evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index), and calibration curve. GSE44001 and GSE52903 were used for external validation. Results: We established a cellular senescence-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of CC patients in the TCGA database. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better overall survival (OS, P =2.021e-05). The area under the ROC curve (AUC) of this model was 0.743 for OS. Multivariate analysis found that the 6-gene risk signature (HR=3.166, 95%CI: 1.660-6.041, P<0.001) was an independent risk factor for CC patients. We then designed an OS-associated nomogram that included the risk signature and clinicopathological factors. The AUC reached 0.860 for predicting 5-year OS. The nomogram showed excellent consistency between the predictions and actual survival observations. Two external GEO validations were corresponding to the gene expression pattern in TCGA. Conclusions: Our results suggested a six-senescence related signature and established a prognostic nomogram that reliably predicted the overall survival for CC. These findings may be beneficial to personalized treatment and medical decision-making.

The effect of telomeres in cervical cancer

“…To investigate the data structure and pattern further, we might examine the differences in the expression of telomere-related genes between normal tissues and tissues from cervical cancer. The heat map and volcano was mapped using "pheatmap", "survminer, survival" to identify the telomere genes that were signi cantly related to prognosis 13 . Utilizing STRING's protein-protein interaction (PPI) feature (https://cn.string-db.org), each clinically signi cant module was equipped with a PPI network for potential biomarker genes, which was then visualized using R. Additionally, gene and genome ontology enrichment (GO) is facilitated by Kyoto Encyclopedia (KEGG pathway analysis) and the INPUT2.0 website (http://cbcb.cdutcm.edu.cn/INPUT/).…”