Background
Bladder cancer (BC) is the ninth most common carcinoma worldwide. Due to no improvement in treatment and survival over the past three decades, it is crucial to construct a robust model for risk assessment, prognosis prediction and refinement of therapy in clinical practice. The autophagy-related genes, with a key role in cancer biology, could have potential for prediction of survival or assistance in decision-making in treatment of bladder cancer.
Methods
Level 3 mRNA sequencing data from The Cancer Genome Atlas-Bladder Urothelial Carcinoma (TCGA-BLCA) was downloaded. We obtained 51 autophagy-related genes after survival analysis. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were conducted and a prognostic signature was established. We validated it in GSE13507 from Gene Expression Omnibus and explored the six genes’ methylation levels and their relationships with immune microenvironment and immune cells infiltration in online databases. The signature and independent clinical characteristics were integrated as a nomogram to facilitate treatment decision-making.
Results
A six-gene prognostic signature was constructed and stratified patients with BC into high-risk and low-risk groups. Meanwhile, it showed a good performance in overall survival prediction. Moreover, we found aberrant methylation in these genes and associations between them and tumor immune microenvironment and immune cells infiltration. Last, we demonstrated the independence of this signature from clinical parameters and a great value in treatment decision-making after its integrating with independent clinical factors.
Conclusion
The proposed six-gene signature showed promise for risk assessment and individualized survival prediction of BC and a nomogram based on it may facilitate the refinement of therapy.
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This is a list of supplementary files associated with this preprint. Click to download.
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Posted 04 Feb, 2020
Posted 04 Feb, 2020
Background
Bladder cancer (BC) is the ninth most common carcinoma worldwide. Due to no improvement in treatment and survival over the past three decades, it is crucial to construct a robust model for risk assessment, prognosis prediction and refinement of therapy in clinical practice. The autophagy-related genes, with a key role in cancer biology, could have potential for prediction of survival or assistance in decision-making in treatment of bladder cancer.
Methods
Level 3 mRNA sequencing data from The Cancer Genome Atlas-Bladder Urothelial Carcinoma (TCGA-BLCA) was downloaded. We obtained 51 autophagy-related genes after survival analysis. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were conducted and a prognostic signature was established. We validated it in GSE13507 from Gene Expression Omnibus and explored the six genes’ methylation levels and their relationships with immune microenvironment and immune cells infiltration in online databases. The signature and independent clinical characteristics were integrated as a nomogram to facilitate treatment decision-making.
Results
A six-gene prognostic signature was constructed and stratified patients with BC into high-risk and low-risk groups. Meanwhile, it showed a good performance in overall survival prediction. Moreover, we found aberrant methylation in these genes and associations between them and tumor immune microenvironment and immune cells infiltration. Last, we demonstrated the independence of this signature from clinical parameters and a great value in treatment decision-making after its integrating with independent clinical factors.
Conclusion
The proposed six-gene signature showed promise for risk assessment and individualized survival prediction of BC and a nomogram based on it may facilitate the refinement of therapy.
Figure 2
Figure 4
Figure 6
Figure 8
Figure 10
Figure 12
Figure 14
Figure 16
This is a list of supplementary files associated with this preprint. Click to download.
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