OCIAD2 as a novel prognostic and therapeutic biomarker for pancreatic cancer: A study based on transcriptomic signature and bioinformatics analysis.

IF 3.6 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
PLoS Computational Biology Pub Date : 2025-10-07 eCollection Date: 2025-10-01 DOI:10.1371/journal.pcbi.1013566
Zhongyuan Cui, Xia Lei, Yani Gou, Zhixian Wu, Xiaojun Huang
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引用次数: 0

Abstract

Background: It is urgent to explore the potential biomarkers for pancreatic cancer (PC) prognosis and treatment to improve patients' outcomes.

Methods: Firstly, we performed an integrated bioinformatics analysis based on extensive transcriptome data from 615 PC tumors and 329 adjacent tissues, screening for genes with prognostic value. We then validated the prognostic value of OCIAD2, DCBLD2, and SAMD9 in different datasets and analyzed their expression levels in single-cell sequencing datasets of normal, paracancer, primary, and metastatic tissues. Next, we further explored the carcinogenic effect after knocking down the expression of OCIAD2 in PC cancer cell line. Finally, a drug sensitivity analysis was conducted.

Results: Differentially expressed genes (DEGs) analysis identified 22 DEGs: ACSL5, ANTXR1, AP1S3, ATP2C2, B3GNT5, C15orf48, CAPG, CTSK, DAPP1, DCBLD2, GPX8, HEPH, IFI44, KRT23, NCF2, OCIAD2, SAMD9, SLC39A10, ST6GALNAC1, TBC1D2, TMSB10 and TSPAN5 with prognostic value in PC, though the related function and mechanism are still unclear. Single-cell sequencing results indicated that OCIAD2 was prominently expressed in ductal cells of primary and metastatic tumors. The expression levels of OCIAD2 mRNA and protein were the highest in pancreatic tumor tissues. Mechanism studies revealed that STAT1 and STAT2 in the JAK-STAT pathway and CCND1, CDK1, and CDK2 in the cell cycle pathway were significantly down-regulated after OCIAD2 knockdown. Drug sensitivity analysis identified 25 compounds significantly associated with OCIAD2.

Conclusions: These results indicate that OCIAD2 is a potential prognostic biomarker and therapeutic target for PC patients.

OCIAD2作为一种新的胰腺癌预后和治疗生物标志物:基于转录组特征和生物信息学分析的研究
背景:迫切需要探索胰腺癌预后和治疗的潜在生物标志物,以改善胰腺癌患者的预后。方法:首先,我们基于615例PC肿瘤和329例癌旁组织的广泛转录组数据进行综合生物信息学分析,筛选具有预后价值的基因。然后,我们在不同的数据集中验证了OCIAD2、dccbld2和SAMD9的预后价值,并分析了它们在正常、癌旁、原发和转移组织的单细胞测序数据集中的表达水平。接下来,我们进一步探讨敲低OCIAD2在PC癌细胞中的表达后的致癌作用。最后进行药敏分析。结果:差异表达基因(DEGs)分析发现,ACSL5、ANTXR1、AP1S3、ATP2C2、B3GNT5、C15orf48、CAPG、CTSK、DAPP1、dbld2、GPX8、HEPH、IFI44、KRT23、NCF2、OCIAD2、SAMD9、SLC39A10、ST6GALNAC1、TBC1D2、TMSB10和TSPAN5等22个基因在PC中具有预后价值,但相关功能和机制尚不清楚。单细胞测序结果显示,OCIAD2在原发和转移性肿瘤的导管细胞中显著表达。OCIAD2 mRNA和蛋白在胰腺肿瘤组织中的表达水平最高。机制研究发现,OCIAD2敲低后,JAK-STAT通路中的STAT1、STAT2和细胞周期通路中的CCND1、CDK1、CDK2均显著下调。药物敏感性分析鉴定出25种与OCIAD2显著相关的化合物。结论:这些结果表明OCIAD2是PC患者潜在的预后生物标志物和治疗靶点。
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来源期刊
PLoS Computational Biology
PLoS Computational Biology BIOCHEMICAL RESEARCH METHODS-MATHEMATICAL & COMPUTATIONAL BIOLOGY
CiteScore
7.10
自引率
4.70%
发文量
820
审稿时长
2.5 months
期刊介绍: PLOS Computational Biology features works of exceptional significance that further our understanding of living systems at all scales—from molecules and cells, to patient populations and ecosystems—through the application of computational methods. Readers include life and computational scientists, who can take the important findings presented here to the next level of discovery. Research articles must be declared as belonging to a relevant section. More information about the sections can be found in the submission guidelines. Research articles should model aspects of biological systems, demonstrate both methodological and scientific novelty, and provide profound new biological insights. Generally, reliability and significance of biological discovery through computation should be validated and enriched by experimental studies. Inclusion of experimental validation is not required for publication, but should be referenced where possible. Inclusion of experimental validation of a modest biological discovery through computation does not render a manuscript suitable for PLOS Computational Biology. Research articles specifically designated as Methods papers should describe outstanding methods of exceptional importance that have been shown, or have the promise to provide new biological insights. The method must already be widely adopted, or have the promise of wide adoption by a broad community of users. Enhancements to existing published methods will only be considered if those enhancements bring exceptional new capabilities.
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