Background:Centrosome amplification, a hallmark of cell cycle dysregulation, drives carcinogenesis through aneuploidy induction and invasive phenotype acquisition. In pancreatic adenocarcinoma—a malignancy characterized by profound genomic instability—the molecular circuitry of centrosome amplification remains enigmatic. Critical gaps persist in understanding its spatiotemporal dynamics in tumor microenvironment remodeling and therapy resistance.Methods:This study integrated centrosome amplification-related genes from TCGA and Genecards, established a prognostic risk model through univariate Cox regression–LASSO penalized Cox regression–multivariate Cox regression analyses, and validated it using GEO datasets. Single-cell sequencing analyses dissected transcriptional heterogeneity and intercellular communication networks, while spatially resolved transcriptomics unveiled spatiotemporal expression patterns and molecular regulatory mechanisms of core genes. With further experimental validation via PCR analysis of patient-derived tissue samples confirming key gene expression patterns.Results:This study identified 23 centrosome amplification-related prognostic genes in pancreatic adenocarcinoma, establishingIFI27,KIF20A,KLK10,SPINK7, andTOP2Aas highly specific diagnostic and prognostic biomarkers. The constructed signature was established as an independent prognostic indicator correlating with aggressive clinicopathological characteristics and chemoresistance. Mechanistically linked to enhanced DNA repair capacity and accelerated cell cycle progression, also synergizes with KRAS mutational profiles. Tumor microenvironment analysis revealed significant associations with immunosuppressive. Single-cell resolution demonstrated cellular specificity of IFI27/KLK10 in ductal epithelial cells and fibroblasts, with intercellular communication networks exhibiting multidimensional regulatory features. Spatially resolved transcriptomics delineated tumor-region-specific expression patterns of core genes. While PCR validation on matched tumor/normal tissues confirmed significant differential expression ofIFI27,KIF20A,KLK10, andTOP2A.Conclusions:This study deciphers the multidimensional clinic–molecular network orchestrated by centrosome amplification in PDAC, revealing its dual-pathogenic mechanism in fueling tumor aggressiveness through coordinated induction of genomic instability and immunosuppressive microenvironment reprogramming. These findings establish a translational framework for developing centrosome dynamics-based prognostic stratification and molecularly targeted therapeutic strategies.
背景：中心体扩增作为细胞周期失调的标志，通过诱导非整倍体和获得侵袭表型驱动肿瘤发生。在胰腺腺癌——一种以显著基因组不稳定性为特征的恶性肿瘤中，中心体扩增的分子调控网络仍不明确。其在肿瘤微环境重塑和治疗抵抗中的时空动态机制尚存关键认知空白。 方法：本研究整合TCGA和Genecards数据库中的中心体扩增相关基因，通过单因素Cox回归–LASSO惩罚Cox回归–多因素Cox回归分析构建预后风险模型，并利用GEO数据集进行验证。单细胞测序分析解析了转录异质性和细胞间通讯网络，空间转录组学则揭示了核心基因的时空表达模式与分子调控机制。进一步通过患者组织样本的PCR分析进行实验验证，确认关键基因表达模式。 结果：本研究在胰腺腺癌中鉴定出23个中心体扩增相关预后基因，确立IFI27、KIF20A、KLK10、SPINK7和TOP2A为高特异性诊断与预后生物标志物。构建的特征模型被确立为独立预后指标，与侵袭性临床病理特征及化疗耐药相关。机制上，该特征与增强的DNA修复能力和加速的细胞周期进程相关，并与KRAS突变谱产生协同效应。肿瘤微环境分析显示其与免疫抑制状态显著相关。单细胞分辨率分析揭示了IFI27/KLK10在导管上皮细胞和成纤维细胞中的细胞特异性表达，其细胞间通讯网络呈现多维调控特征。空间转录组学描绘了核心基因在肿瘤区域的特异性表达模式。配对肿瘤/正常组织的PCR验证证实了IFI27、KIF20A、KLK10和TOP2A的显著差异表达。 结论：本研究解析了中心体扩增在胰腺导管腺癌中构建的多维临床-分子网络，揭示了其通过协同诱导基因组不稳定性和免疫抑制微环境重编程驱动肿瘤侵袭性的双重致病机制。这些发现为开发基于中心体动力学的预后分层和分子靶向治疗策略建立了转化框架。
肿瘤(癌症)患者之家