Proteomics-based Model for Predicting the Risk of Brain Metastasis in Patients with Resected Lung Adenocarcinoma carrying the EGFR Mutation

基于蛋白质组学的模型预测携带 EGFR 突变的切除性肺腺癌患者脑转移风险

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作者:Qiuhua Deng, Fengnan Wang, Lei Song, Liangyu Chen, Ying Huang, Zhihua Guo, Haihong Yang

Conclusions

A predictive model based on protein markers was developed to accurately predict postoperative BM in operable LUAD harboring EGFR mutation.

Methods

We conducted a retrospective study of BMs in postoperative recurrent LUAD with EGFR mutation in the First Affiliated Hospital of Guangzhou Medical University. Tissue proteomic analysis was applied in the primary tumors of resected LUAD in this study using liquid chromatography-mass spectrometry (LC-MS/MS). To identify potential markers for predicting LUAD BM, comparative analyses were performed on different groups to evaluate proteins associated with high risk of BMs.

Results

A combination of three potential marker proteins was found to discriminate well between distal metastasis (DM) and local recurrence (LR) of postoperative LUAD with EGFR mutation. Gene Ontology (GO) analysis of significantly altered proteins between BM and non-BM (NBM) indicated that lipid metabolism and cell cycle-related pathways were involved in BMs of LUAD. And the enriched pathways correlated with BMs were found to be quite different in the comparison groups of postoperative adjuvant therapy, tyrosine kinase inhibitor (TKI), and chemotherapy groups. Finally, we developed a random forest algorithm model with eight proteins (RRS1, CPT1A, DNM1, SRCAP, MLYCD, PCID2, IMPAD1 and FILIP1), which showed excellent predictive value (AUC: 0.9401) of BM in patients with LUAD harboring EGFR mutation. Conclusions: A predictive model based on protein markers was developed to accurately predict postoperative BM in operable LUAD harboring EGFR mutation.

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