Comprehensive Analysis of Tertiary Lymphoid Structures in Pancreatic Cancer: Molecular Characteristics and Prognostic Implications

IF 0.5 4区生物学 Q4 BIOCHEMICAL RESEARCH METHODS

Current Proteomics Pub Date : 2024-09-02 DOI:10.2174/0115701646317271240821071544

Jiana Fang, Jingru Huang, Jiazhong Zhang, Lin Chen, Jin Deng

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引用次数: 0

Abstract

Purpose: The molecular properties of TLSs in pancreatic cancer are still not well comprehended. This research delved into the molecular properties of intratumoral TLSs in pancreatic cancer through the exploration of multi-omics data. Methods: Seven key genes were identified through Cox regression analysis and random survival forest analysis from a total of 5908 genes related to TLSs. These genes were utilized to construct a prognosis model, which was subsequently validated in two independent cohorts. Additionally, the study investigated the molecular features of different populations of TLSs from multiple perspectives. The model’ s forecasting accuracy was verified by analyzing column-line graphs and decision curves, taking into account the patients’ clinical traits. Results: The analysis of immune cell infiltration showed a notably greater presence of Macrophage M0 cells in the group at high risk than in the low-risk group. The pathway enrichment analysis demonstrated the activation among common cancer-related pathways, including ECM receptor interaction, pathways in cancer, and focal adhesion, in the high-risk group. Additionally, the methylation study revealed notable disparities in DNA methylation between two TLS groups across four regions: TSS200, 5’ UTR, 1stExon, and Body. A variety of notably distinct sites were linked with PVT1. Furthermore, by constructing a competing endogenous RNA network, several mRNAs and lncRNAs were identified that compete for the binding of hsa-mir-221. Conclusion: Overall, this research sheds light on the molecular properties of TLSs across various pancreatic cancer stages and suggests possible focal points for the treatment of pancreatic cancer. result: The analysis of immune cell infiltration showed a notably greater presence of Macrophage M0 cells in the group at high-risk than in the low-risk group. Pathway enrichment analysis demonstrated the activation among common cancer-related pathways, including ECM receptor interaction, pathways in cancer, and focal adhesion, in the high-risk group. Additionally, the methylation study revealed notable disparities in DNA methylation between two TLSs groups across four regions: TSS200, 5’ UTR, 1stExon, and Body. A variety of notably distinct sites were linked with PVT1. By constructing a competing endogenous RNA network, multiple mRNAs and lncRNAs competing for the binding of hsa-mir-221 were identified.

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胰腺癌三级淋巴结构的综合分析：分子特征和预后意义

目的：胰腺癌TLS的分子特性仍未得到很好的理解。本研究通过多组学数据探索胰腺癌瘤内 TLS 的分子特性。研究方法通过Cox回归分析和随机生存森林分析，从5908个与TLSs相关的基因中确定了7个关键基因。利用这些基因构建了一个预后模型，随后在两个独立队列中进行了验证。此外，该研究还从多个角度研究了不同TLS群体的分子特征。考虑到患者的临床特征，通过分析柱状线图和决策曲线验证了该模型的预测准确性。结果显示对免疫细胞浸润的分析表明，与低风险组相比，高风险组中巨噬细胞 M0 的数量明显增多。通路富集分析表明，在高风险组中，常见的癌症相关通路被激活，包括 ECM 受体相互作用、癌症通路和病灶粘附。此外，甲基化研究显示，两个 TLS 组之间的 DNA 甲基化在四个区域存在显著差异：TSS200、5' UTR、1stExon 和 Body。多个明显不同的位点与 PVT1 有关。此外，通过构建竞争性内源性 RNA 网络，发现了几个 mRNA 和 lncRNA 与 hsa-mir-221 竞争结合。结论总之，这项研究揭示了胰腺癌各期TLS的分子特性，并提出了治疗胰腺癌的可能焦点：对免疫细胞浸润的分析表明，高危组中巨噬细胞 M0 细胞的存在明显多于低危组。通路富集分析表明，在高风险组中，常见的癌症相关通路被激活，包括 ECM 受体相互作用、癌症通路和病灶粘附。此外，甲基化研究还发现，两个 TLSs 组间的 DNA 甲基化在四个区域存在明显差异：TSS200、5' UTR、1stExon 和 Body。多个明显不同的位点与 PVT1 有关。通过构建内源性 RNA 竞争网络，发现了多个 mRNA 和 lncRNA 竞争 hsa-mir-221 的结合。

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来源期刊

Current Proteomics BIOCHEMICAL RESEARCH METHODS-BIOCHEMISTRY & MOLECULAR BIOLOGY

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

>0 weeks

期刊介绍： Research in the emerging field of proteomics is growing at an extremely rapid rate. The principal aim of Current Proteomics is to publish well-timed in-depth/mini review articles in this fast-expanding area on topics relevant and significant to the development of proteomics. Current Proteomics is an essential journal for everyone involved in proteomics and related fields in both academia and industry. Current Proteomics publishes in-depth/mini review articles in all aspects of the fast-expanding field of proteomics. All areas of proteomics are covered together with the methodology, software, databases, technological advances and applications of proteomics, including functional proteomics. Diverse technologies covered include but are not limited to: Protein separation and characterization techniques 2-D gel electrophoresis and image analysis Techniques for protein expression profiling including mass spectrometry-based methods and algorithms for correlative database searching Determination of co-translational and post- translational modification of proteins Protein/peptide microarrays Biomolecular interaction analysis Analysis of protein complexes Yeast two-hybrid projects Protein-protein interaction (protein interactome) pathways and cell signaling networks Systems biology Proteome informatics (bioinformatics) Knowledge integration and management tools High-throughput protein structural studies (using mass spectrometry, nuclear magnetic resonance and X-ray crystallography) High-throughput computational methods for protein 3-D structure as well as function determination Robotics, nanotechnology, and microfluidics.