The value of a metabolic and immune-related gene signature and adjuvant therapeutic response in pancreatic cancer

代谢和免疫相关基因特征及辅助治疗反应在胰腺癌中的价值

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作者:Danlei Ni #, Jiayi Wu #, Jingjing Pan, Yajing Liang, Zihui Xu, Zhiying Yan, Kequn Xu, Feifei Wei

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal prognosis. Treatment outcomes exhibit substantial variability across patients, underscoring the urgent need for robust predictive models to effectively estimate survival probabilities and therapeutic responses in PDAC.

Conclusion

This 8-gene signature enhances prognostic accuracy and therapeutic decision-making in PDAC, offering valuable insights for clinical applications and personalized treatment strategies.

Methods

Metabolic and immune-related genes exhibiting differential expression were identified using the TCGA-PDAC and GTEx datasets. A genetic prognostic model was developed via univariable Cox regression analysis on a training cohort. Predictive accuracy was assessed using Kaplan-Meier (K-M) curves, calibration plots, and ROC curves. Additional analyses, including GSAE and immune cell infiltration studies, were conducted to explore relevant biological mechanisms and predict therapeutic efficacy.

Results

An 8-gene prognostic model (AK2, CXCL11, TYK2, ANGPT4, IL20RA, MET, ENPP6, and CA12) was established. Three genes (AK2, ENPP6, and CA12) were associated with metabolism, while the others were immune-related. Most genes correlated with poor prognosis. Validation in TCGA-PDAC and GSE57495 datasets demonstrated robust performance, with AUC values for 1-, 3-, and 5-year OS exceeding 0.7. The model also effectively predicted responses to adjuvant therapy.

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