胃癌双硫死亡相关lncRNA预后模型的建立与应用
Establishment and application of a prognostic model for disulfidptosis-associated lncRNA in gastric cancer
投稿时间:2024-08-20  修订日期:2024-11-11
DOI:
中文关键词:  双硫死亡  胃癌  TCGA  预后模型
英文关键词:Disulfidptosis  Gastric cancer  TCGA  Prognostic model
基金项目:
作者单位邮编
胡巾帼* 浙江中医药大学附属杭州市中医院 310000
朱轶天 浙江中医药大学附属杭州市中医院 
沈一杰 浙江中医药大学附属杭州市中医院 
沈榕 浙江中医药大学附属杭州市中医院 
沈文军 浙江中医药大学附属杭州市中医院 
张璇 浙江中医药大学附属杭州市中医院 
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中文摘要:
      目的:胃癌是肿瘤相关死亡主要原因之一,对胃癌风险评估方法的优化具有积极的临床意义。虽然有研究表明,双硫死亡作为一种新的细胞程序性死亡,在胃癌中具有潜在的作用,但是其在胃癌中的具体机制尚不完全清楚,仍需进行进一步探索。
英文摘要:
      Abstract: OBJECTIVE: Gastric cancer is one of the major causes of tumor-related deaths, and the optimization of risk assessment methods for gastric cancer has positive clinical significance. Although it has been shown that disulfide death, as a new type of programmed cell death, has a potential role in gastric cancer, its specific mechanism in gastric cancer is not fully understood and further exploration is still needed. METHODS: Information on gastric cancer patients was obtained from The Cancer Genome Atlas (TCGA) dataset. Dual sulfur death-related genes were obtained from the literature, and Pearson correlation analysis was performed to identify dual sulfur death-related lncRNAs (DPL). We performed machine learning algorithms for DPL, one-factor Cox and least absolute shrinkage and selection operator (Lasso) analyses to obtain DPL associated with prognostic traits,and multifactorial Cox analyses to identify DPL with independent prognostic value.Dual-sulfur death-associated lncRNA prognostic genes were verified by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) in normal gastric epithelial mucosa cell skin cell line (GSE-1) and gastric cancer cell lines (AZ521, MKN45, MGC-803) were differentially expressed among the three cell lines. Then, clinical subgroups, tumor mutation load (TMB) assay, drug sensitivity analysis, immune infiltration and pathway enrichment analysis were further analyzed to comprehensively explore the clinical significance. RESULTS: In this study, six DPLs associated with clinical outcome in gastric cancer were obtained using Lasso-one-way Cox analysis and multifactorial Cox analysis. and these lncRNAs were confirmed to be independent prognostic factors in gastric cancer (IGFL2-AS1, AC129507.1, PINK1-AS, TNFRSF10A-AS1, AC000123.1, FLNB-AS1). Subsequently, a prognostic model of gastric cancer was constructed based on the above six lncRNAs, and the reliability of the model was verified. Survival analysis showed that the overall survival of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. Immune infiltration and drug sensitivity analyses showed significant differences between different risk groups. In addition, the qRT-PCR results suggested that the expression levels of AC129507.1 and TNFRSF10A-AS1 genes were significantly higher in all three gastric cancer cell lines than in GSE-1 cell line (P < 0.05). Other genes showed different levels of expression in normal and tumor cell lines. CONCLUSION: A new prognostic model based on disulfide death-related lncRNAs can be used for prognostic prediction and precise treatment of gastric cancer.
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