关键词: 铜死亡, 长链非编码 RNA, 胰腺癌, 预后模型, 免疫浸润, 中药

Abstract:

Objective A prognostic model for pancreatic cancer(PC) based on cuproptosis-related long noncoding RNA (CRL) was constructed to predict the traditional Chinese medicine that regulates cuproptosis- related gene(CRG). Method A risk model for forecasting PC prognosis was constructed by utilizing Cox regression and Pearson correlation analysis, utilizing clinical data and RNA-seqs of 183 PC patients sourced from theTCGA. Screening CRL through LASSO regression, and the nomogram was formed by uniting the risk score and clinical features. To test the model's accuracy, receiver operator characteristic curve (ROC) and C-index were employed. An assessment was made of the correlation between risk scores and immunoinfi ltration and chemotherapy/targeted agents. The potential Chinese medicines for controlling CRG were predicted through the utilization of Coremine Medical database. Result The PC risk model was developed based on the risk scores of six CRLs (MIR1915HG, PRECSIT, AC004982.1, AC023043.4, AC010999.2, FOXCUT).The AUC for forecasting 1-year, 3-year and 5-year survival rates in PC patients was 0.782, 0.786 and 0.912 respectively, as revealed by the risk model, surpassing age, grade and TNM stage. A relationship was found between the risk score and the enrichment of tumor-infi ltrating lymphocytes, the presence of regulatory T cells, and the sensitivity of fourteen chemotherapeutic/targeted drugs. There are ninety-eight Chinese medicines that potentially regulate CRG; their eff ects primarily involve heat clearing and detoxifying properties attributed mainly to liver spleen and lung meridians. Traditional Chinese medicine Tenacissoside may have potential regulatory effects on key gene FDX1 involved in copper death mechanism. Conclusion A risk signature constructed based on six CRLs could assess the prognosis and immunity of PC, and Tenacissoside may have important regulatory effi cacy on the mechanism of coppercuproptosis.

Key words: Cuproptosis, Long noncoding RNA, Pancreatic cancer, Prognostic signature, Immuneinfi ltration, Traditional Chinese medicine