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建立和验证与胰腺导管腺癌预后相关的泛素化相关基因特征。

Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.

机构信息

Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.

Department of Emergency, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.

出版信息

Front Immunol. 2023 Jun 9;14:1171811. doi: 10.3389/fimmu.2023.1171811. eCollection 2023.

Abstract

BACKGROUND

Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients' prognoses.

METHODS

The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.

RESULTS

The URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.

CONCLUSION

The URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.

摘要

背景

胰腺导管腺癌(PDAC)患者的预后因众多变量而异。然而,需要进一步的研究来揭示泛素化相关基因(URG)对确定 PDAC 患者预后的潜在影响。

方法

通过共识聚类发现 URG 聚类,利用 TCGA-PAAD 数据的最小绝对收缩和选择算子(LASSO)回归分析,对跨聚类的预后差异表达基因(DEG)进行分析,以建立特征。在 TCGA-PAAD、GSE57495 和 ICGC-PACA-AU 中进行验证分析,以显示特征的稳健性。使用 RT-qPCR 验证风险基因的表达。最后,我们制定了一个列线图来提高我们预测工具的临床疗效。

结果

开发了由三个基因组成的 URG 特征,该特征与 PAAD 患者的预后高度相关。该列线图是通过将 URG 特征与临床病理特征相结合建立的。我们发现 URG 特征明显优于其他单个预测因子(年龄、分级、T 分期等)。此外,免疫微环境分析表明,低风险组的 ESTIMATEscore、ImmuneScores 和 StromalScores 升高。两组之间浸润组织的免疫细胞不同,免疫相关基因的表达也不同。

结论

URG 特征可作为 PDAC 患者预后的生物标志物,并为其选择合适的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/10289160/3d78dedecbd5/fimmu-14-1171811-g001.jpg

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