Integrating Machine Learning and Mendelian Randomization Determined a Functional Neurotrophin-Related Gene Signature in Patients with Lower-Grade Glioma.
Cong ZhangGuichuan LaiJielian DengKangjie LiLiuyi ChenXiaoni ZhongBiao XiePublished in: Molecular biotechnology (2024)
Recent researches reported that neurotrophins can promote glioma growth/invasion but the relevant model for predicting patients' survival in Lower-Grade Gliomas (LGGs) lacked. In this study, we adopted univariate Cox analysis, LASSO regression, and multivariate Cox analysis to determine a signature including five neurotrophin-related genes (NTGs), CLIC1, SULF2, TGIF1, TTF2, and WEE1. Two-sample Mendelian Randomization (MR) further explored whether these prognostic-related genes were genetic variants that increase the risk of glioma. A total of 1306 patients have been included in this study, and the results obtained from the training set can be verified by four independent validation sets. The low-risk subgroup had longer overall survival in five datasets, and its AUC values all reached above 0.7. The risk groups divided by the NTGs signature exhibited a distinct difference in targeted therapies from the copy-number variation, somatic mutation, LGG's surrounding microenvironment, and drug response. MR corroborated that TGIF1 was a potential causal target for increasing the risk of glioma. Our study identified a five-NTGs signature that presented an excellent survival prediction and potential biological function, providing new insight for the selection of LGGs therapy.
Keyphrases
- copy number
- end stage renal disease
- machine learning
- ejection fraction
- newly diagnosed
- chronic kidney disease
- genome wide
- mitochondrial dna
- stem cells
- randomized controlled trial
- prognostic factors
- dna methylation
- computed tomography
- risk assessment
- artificial intelligence
- patient reported
- patient reported outcomes
- big data
- deep learning
- human health
- bone marrow
- single cell
- adverse drug
- drug induced
- phase iii
- clinical evaluation