Xia Jie, Zheng Linyong, Zhang Huarong, Fan Qi, Liu Hui, Wang Ouxi, Yan Haidan
School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China.
Fujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350100, China.
Int J Mol Sci. 2025 Apr 22;26(9):3936. doi: 10.3390/ijms26093936.
The high heterogeneity between patients can complicate the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we explored the association of universally differentially expressed genes (UDEGs) with resistance to chemotherapy and immunotherapy in the context of pancreatic cancer. In this work, sixteen up-regulated and three down-regulated genes that were dysregulated in more than 85% of 102 paired and 5% of 521 unpaired PDAC samples were identified and defined as UDEGs. A single-cell level analysis further validated the high expression levels of the up-UDEGs and the low levels of the down-UDEGs in cancer-related ductal cells, which could represent the malignant changes seen in pancreatic cancer. Based on a drug sensitivity analysis, we found that , and are closely related to the resistance mechanism of PDAC, and their high expression predicted worse survival for PDAC patients. This suggests that targeting these genes could be a potential way to reduce drug resistance and improve survival. Based on the immune infiltration analysis, the abnormal expression of the UDEGs was found to be related to the formation of an immunosuppressive tumor microenvironment. In conclusion, these UDEGs are common features of PDAC and could be involved in the resistance of pancreatic cancer and might serve as novel drug targets to guide research into drug repurposing.
患者之间的高度异质性会使胰腺导管腺癌(PDAC)的诊断和治疗复杂化。在此,我们在胰腺癌背景下探讨了普遍差异表达基因(UDEGs)与化疗和免疫治疗耐药性之间的关联。在这项研究中,我们鉴定出16个上调基因和3个下调基因,这些基因在102对PDAC样本的85%以上以及521个非配对PDAC样本的5%以上中表达失调,并将其定义为UDEGs。单细胞水平分析进一步验证了上调UDEGs在癌症相关导管细胞中的高表达水平以及下调UDEGs的低表达水平,这可能代表了胰腺癌中出现的恶性变化。基于药物敏感性分析,我们发现 、 和 与PDAC的耐药机制密切相关,它们的高表达预示着PDAC患者的生存预后较差。这表明靶向这些基因可能是降低耐药性和改善生存的潜在途径。基于免疫浸润分析,发现UDEGs的异常表达与免疫抑制性肿瘤微环境的形成有关。总之,这些UDEGs是PDAC的共同特征,可能参与胰腺癌的耐药过程,并可能作为新型药物靶点来指导药物再利用研究。