膜联蛋白A9(ANXA9)在结直肠癌中的表达及其对免疫逃逸和耐药性的影响的临床意义
Clinical significance of ANXA9 expression in colorectal cancer and its impact on immune evasion and drug resistance.
作者信息
Hong Mingyang, Dong Qian, Zhu Huiming, Huang Xu
机构信息
Laboratory Department of the Affiliated, Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China.
Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, 226018, Jiangsu, China.
出版信息
Discov Oncol. 2025 Sep 1;16(1):1664. doi: 10.1007/s12672-025-03477-0.
BACKGROUND
Colorectal cancer (CRC) is a major global health challenge, creating an urgent need to find new biomarkers that improve early detection and treatment success. While studies suggest that ANXA9 contributes to cancer development, its expression in CRC and its links to prognosis, immune evasion, and resistance are poorly understood.
METHODS
This study conducted bioinformatics analysis of gene expression data from the TCGA and GEO to evaluate the prognostic and diagnostic potential of ANXA9. Kaplan-Meier survival analysis and ROC curves were employed to assess these capabilities. Furthermore, ANXA9 gene mutations were examined using cBioPortal, and promoter methylation levels were analyzed via UALCAN. Enrichment, immune infiltration, and treatment response analyses were also performed on ANXA9.
RESULTS
Our research demonstrates that ANXA9 expression is significantly elevated in CRC tissues compared to normal tissues. This elevation is associated with pathological staging and TNM classification. Kaplan-Meier analysis reveals that increased ANXA9 levels are correlated with reduced overall survival and disease-specific survival. Furthermore, several mutations in ANXA9 have been identified, accompanied by a significant reduction in promoter methylation levels. Genes related to ANXA9 are significantly enriched in pathways involved in immune responses, such as cytokine secretion and T cell activation. We also observed a correlation between ANXA9 expression and the infiltration of immune cells, particularly M1 macrophages. ANXA9 expression is linked to increased levels of the immune checkpoint gene IGSF8 and resistance to chemotherapeutic agents.
CONCLUSION
This study reveals the critical role of ANXA9 in colorectal cancer. Its increased expression is closely associated with poor prognosis, immune evasion, and chemotherapy resistance. This provides valuable evidence for future clinical research and treatment strategies.
背景
结直肠癌(CRC)是一项重大的全球健康挑战,迫切需要找到能够改善早期检测和治疗效果的新生物标志物。虽然研究表明膜联蛋白A9(ANXA9)促进癌症发展,但其在结直肠癌中的表达及其与预后、免疫逃逸和耐药性的联系仍知之甚少。
方法
本研究对来自TCGA和GEO的基因表达数据进行了生物信息学分析,以评估ANXA9的预后和诊断潜力。采用Kaplan-Meier生存分析和ROC曲线来评估这些能力。此外,使用cBioPortal检查ANXA9基因突变,并通过UALCAN分析启动子甲基化水平。还对ANXA9进行了富集、免疫浸润和治疗反应分析。
结果
我们的研究表明,与正常组织相比,CRC组织中ANXA9表达显著升高。这种升高与病理分期和TNM分类相关。Kaplan-Meier分析显示,ANXA9水平升高与总生存期和疾病特异性生存期降低相关。此外,已鉴定出ANXA9的几种突变,同时启动子甲基化水平显著降低。与ANXA9相关的基因在细胞因子分泌和T细胞活化等免疫反应相关途径中显著富集。我们还观察到ANXA9表达与免疫细胞浸润,特别是M1巨噬细胞浸润之间存在相关性。ANXA9表达与免疫检查点基因IGSF8水平升高和对化疗药物的耐药性有关。
结论
本研究揭示了ANXA9在结直肠癌中的关键作用。其表达增加与预后不良、免疫逃逸和化疗耐药密切相关。这为未来的临床研究和治疗策略提供了有价值的证据。