Integrative Analysis of TLS-Associated Gene Signatures, Immune Infiltration and Drug Sensitivity in Pancreatic Cancer

IF 1.9 4区生物学 Q4 CELL BIOLOGY

IET Systems Biology Pub Date : 2025-09-28 DOI:10.1049/syb2.70038

Mengzhou Gao, Guohui Li, Xin Wang, Xueyun Wang, Danning Tang, Xiang Ao, An Luo, Zhenguo Wen, Teng Wang, Zhaojun Jia

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Abstract

Pancreatic adenocarcinoma (PAAD) remains highly lethal because of chemotherapy resistance and immunosuppressive microenvironments. Tertiary lymphoid structures (TLSs) were analysed in PAAD to develop personalised therapeutic strategies. Nine TLS-related genes (CCR6, CD1d, CD79B, CETP, EIF1AY, LAT, PTGDS, RBP5 and SKAP1) were selected for integrative analysis of TLS status in relation to clinical outcomes, immune cell infiltration, tumour mutational burden (TMB) and drug resistance. High TLS scores (TLS_H) were associated with improved overall survival (OS) and progression-free survival (PFS), independent of age or tumour grade. Twelve immune cell types differed across TLSs. Single-cell RNA-seq analysis revealed that the 9 TLS-related genes were enriched in distinct immune cell populations. Combining TLS and TMB improved survival prediction. Notably, the TLS_H group demonstrated enhanced sensitivity to chemotherapeutics including AZD8055, axitinib, vorinostat, nilotinib, camptothecin and paclitaxel. Real-time fluorescent quantitative PCR (RT-qPCR) validation in Mia PaCa2 and Jurkat cells indicated that LAT, RBP5 and SKAP1 may play important roles in modulating sensitivity to these chemotherapeutics. These findings establish TLS as a potential biomarker for PAAD, enabling personalised chemotherapy selection by integrating immune contexture and genomic drivers to improve clinical outcomes.

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胰腺癌tls相关基因特征、免疫浸润和药物敏感性的综合分析。

由于化疗耐药和免疫抑制微环境，胰腺腺癌（PAAD）仍然具有高致死率。分析PAAD的三级淋巴结构（TLSs），以制定个性化的治疗策略。选择9个TLS相关基因（CCR6、CD1d、CD79B、CETP、EIF1AY、LAT、PTGDS、RBP5和SKAP1），综合分析TLS状态与临床结局、免疫细胞浸润、肿瘤突变负担（TMB）和耐药性的关系。高TLS评分（TLS_H）与改善的总生存期（OS）和无进展生存期（PFS）相关，与年龄或肿瘤分级无关。12种免疫细胞类型在TLSs中存在差异。单细胞RNA-seq分析显示，9个tls相关基因在不同的免疫细胞群中富集。联合TLS和TMB可改善生存预测。值得注意的是，TLS_H组对AZD8055、阿西替尼、伏立诺他、尼罗替尼、喜树碱和紫杉醇等化疗药物的敏感性增强。对Mia PaCa2和Jurkat细胞的实时荧光定量PCR （RT-qPCR）验证表明，LAT、RBP5和SKAP1可能在调节这些化疗药物的敏感性中发挥重要作用。这些发现确立了TLS作为PAAD的潜在生物标志物，通过整合免疫环境和基因组驱动因素来实现个性化化疗选择，以改善临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

IET Systems Biology 生物-数学与计算生物学

CiteScore

4.20

自引率

4.30%

发文量

审稿时长

>12 weeks

期刊介绍： IET Systems Biology covers intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. Papers that analyse genomic data in order to identify variables and basic relationships between them are considered if the results provide a basis for mathematical modelling and simulation of cellular dynamics. Manuscripts on molecular and cell biological studies are encouraged if the aim is a systems approach to dynamic interactions within and between cells. The scope includes the following topics: Genomics, transcriptomics, proteomics, metabolomics, cells, tissue and the physiome; molecular and cellular interaction, gene, cell and protein function; networks and pathways; metabolism and cell signalling; dynamics, regulation and control; systems, signals, and information; experimental data analysis; mathematical modelling, simulation and theoretical analysis; biological modelling, simulation, prediction and control; methodologies, databases, tools and algorithms for modelling and simulation; modelling, analysis and control of biological networks; synthetic biology and bioengineering based on systems biology.