Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness

Frontiers in Pharmacology

Pharmacology

Sheng Tu¹  Yunqing Qiu² 

[1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China;null;

关键词: hepatocellular carcinoma;    Foxo signaling pathway;    molecular subtypes;    prognosis;    treatment assessment;   

DOI  :  10.3389/fphar.2023.1213506

 received in 2023-04-28, accepted in 2023-08-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Transcription factors in Foxo signaling pathway influence hepatocellular carcinoma metastasis through epithelial mesenchymal transition-related pathways. Prognostic factors in the Foxo signaling pathway are feasible for HCC prognosis and therapeutic management.Methods: Based on the differentially expressed genes and Foxo signaling pathway genes in HCC, the ConsensusClusterPlus package was conducted to identify Foxo signaling pathway-related molecular subtypes in HCC. Based on the DEGs in the FMSs, the optimal prognostic factors in HCC were screened by cox and least absolute shrinkage and selection operator (LASSO) cox analysis to form the Foxo prognosis score (FPS). The prognostic predictive effectiveness of FPS was assessed by Kaplan Meier (K-M) analysis and Receiver Operating Characteristic (ROC) analysis. Additionally, tumor microenvironment (TME) score, tumor mutation burden (TMB) and treatment sensitivity differences in FMSs and FPS groups were also evaluated.Results: There were low, medium and high Foxo signaling pathway activity molecular subtypes in HCC named FMS 1, FMS 2 and FMS 3, respectively. FMS 1 with lowest Foxo signaling pathway activity presented an excellent survival advantage, while FMS 3 with highest Foxo signaling pathway activity exhibited an inhibitory TME status. According to FPS grouping, low FPS exhibited favorable survival, low TMB and anti-tumor activity. Patients in the low FPS group were mostly in the early stage of cancer. Moreover, we found that patients with high and low FPS exhibited different sensitivity to chemotherapy, and patients with low FPS were more sensitive to immunotherapy.Conclusion: We revealed a novel molecular subtype and prognostic tool based on Foxo signaling pathway signature, which could potentially provide a direction for accurate and effective assessment of potential personalized treatment options and prognostic management for HCC patients.

【 授权许可】

Unknown   
Copyright © 2023 Tu and Qiu.