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基底膜基因特征的开发及胰腺癌潜在候选治疗靶点的鉴定。

Development of a basement membrane gene signature and identification of the potential candidate therapeutic targets for pancreatic cancer.

作者信息

Lin Kai, Xu Dong, Wang Xiaoxiao, Shi Jun, Gao Wentao

机构信息

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Gastrointestinal Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Gland Surg. 2023 Feb 28;12(2):263-281. doi: 10.21037/gs-23-24. Epub 2023 Feb 27.

Abstract

BACKGROUND

Pancreatic cancer is a deadly cancer with a poor prognosis. In light of mounting evidence that basement membrane genes (BMGs) play a role in the development of cancer, we sought to examine the prognostic importance and role of BMGs in pancreatic ductal adenocarcinoma (PDAC) patients.

METHODS

BMGs were obtained from previous top research studies. The clinical and messenger ribonucleic acid expression data were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets, respectively. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used for the PDAC risk modeling and gene identification. The Kaplan-Meier method was used to compare outcomes between the low- and high-risk groups. Finally, we analyzed small-molecule drugs that could be used to target BMGs for treatment using the Enrichr data set and validated the function of the tubulointerstitial nephritis antigen () in pancreatic cancer.

RESULTS

We successfully constructed and validated a 7 BMG-based model to predict PDAC patient outcomes. Additionally, we discovered that 7 BMG-based model was an independent predictive factor for PDAC. According to our functional analysis, the majority of the signaling pathways enriched in BMGs were those connected to malignancy. Immune cell infiltration and immunological checkpoints were also linked to the BMG-based model. Further, we identified 5 small-molecule drugs that may be useful in treating PDAC patients. We also found that promoted cell proliferation in pancreatic cancer.

CONCLUSIONS

Our study extended understandings of how BMGs work in PDAC. We identified a credible predictive biomarker for PDAC patients' survival.

摘要

背景

胰腺癌是一种预后较差的致命性癌症。鉴于越来越多的证据表明基底膜基因(BMGs)在癌症发展中起作用,我们试图研究BMGs在胰腺导管腺癌(PDAC)患者中的预后重要性和作用。

方法

BMGs来自之前的顶级研究。临床和信使核糖核酸表达数据分别从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据集中获取。采用Cox回归和最小绝对收缩和选择算子(LASSO)回归分析进行PDAC风险建模和基因识别。采用Kaplan-Meier方法比较低风险组和高风险组的预后。最后,我们使用Enrichr数据集分析了可用于靶向BMGs进行治疗的小分子药物,并验证了肾小管间质性肾炎抗原()在胰腺癌中的功能。

结果

我们成功构建并验证了一个基于7个BMG的模型来预测PDAC患者的预后。此外,我们发现基于7个BMG的模型是PDAC的一个独立预测因素。根据我们的功能分析,BMGs中富集的大多数信号通路是与恶性肿瘤相关的通路。免疫细胞浸润和免疫检查点也与基于BMG的模型有关。此外,我们确定了5种可能对治疗PDAC患者有用的小分子药物。我们还发现 促进了胰腺癌中的细胞增殖。

结论

我们的研究扩展了对BMGs在PDAC中作用机制的理解。我们为PDAC患者的生存确定了一个可靠的预测生物标志物。

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