一种新的方法:通过评估坏死样细胞死亡和免疫状态,能够预测胰腺癌的肿瘤微环境和治疗靶点。
A new approach: Evaluation of necroptosis and immune status enables prediction of the tumor microenvironment and treatment targets in pancreatic cancer.
发表日期:2023
作者:
Si-Yuan Lu, Jie Hua, Jiang Liu, Miao-Yan Wei, Chen Liang, Qing-Cai Meng, Bo Zhang, Xian-Jun Yu, Wei Wang, Jin Xu, Si Shi
来源:
Computational and Structural Biotechnology Journal
摘要:
越来越多的证据表明,坏死激活程序与胰腺癌之间存在潜在相关性,并且坏死激活程序、免疫浸润和胰腺癌微环境之间的关系越来越受到关注。然而,基于坏死激活程序和免疫力的二维表型和预后评估系统尚未被探索。在本研究中,我们探索了坏死激活程序相关分子的全癌基因组签名,确定了坏死激活程序相关分子的突变和表达谱,以及表达水平和甲基化/拷贝数变异水平之间的相关性。我们在胰腺癌中确定了独特的坏死激活程序状态和免疫状态,高坏死激活程序表型和高免疫表型均比低坏死激活程序表型和低免疫表型预示着更好的预后。我们构建的二维表型对胰腺癌预后、炎症和免疫微环境具有理想的识别效果。 “高坏死激活程序和高免疫(HNHI)”组显示了最佳预后和最高比例的浸润性免疫细胞。 NI评分可用于预测患者预后,并与免疫微环境评分、化疗药物IC50和肿瘤突变负荷相关。此外,它可能有助于预测个体化化疗和免疫治疗的效果。我们的研究还揭示了SLC2A1与坏死激活程序和免疫力均有关,它在胰腺癌中充当潜在的癌基因。总之,我们开发的二维表型和NI评分是临床多组学应用和预测化疗和免疫治疗反应的有希望的工具,并在胰腺癌患者的精准医学和个体化治疗决策方面带来好处。 © 2023 作者。
Growing evidence indicates a potential correlation between necroptosis and pancreatic cancer, and the relationship between necroptosis, immune infiltration and the microenvironment in pancreatic cancer has drawn increasing attention. However, two-dimensional phenotype and prognostic assessment systems based on a combination of necroptosis and immunity have not been explored. In our present study, we explored the pancancer genomics signature of necroptosis-related molecules, identifying necroptosis-related molecule mutation profiles, expression profiles, and correlations between expression levels and methylation/CNV levels. We identified distinct necroptotic as well as immune statuses in pancreatic cancer, and a high necroptosis phenotype and high immunity phenotype both indicated better prognosis than a low necroptosis phenotype and low immunity phenotype. The two-dimensional phenotype we constructed has ideal discriminative effects on pancreatic cancer prognosis, inflammation, and the immune microenvironment. The "high-necroptosis and high-immunity (HNHI)" group exhibited the best prognosis and the highest proportion of infiltrating immune cells. The NI score can be used to predict patient prognosis and is correlated with the immune microenvironment score, chemotherapeutic drug IC50, and tumor mutational burden. In addition, it may be useful for predicting the effect of individualized chemotherapy and immunotherapy. Our study also revealed that SLC2A1 is associated with both necroptosis and immunity and acts as a potential oncogene in pancreatic cancer. In conclusion, the two-dimensional phenotype and NI score we developed are promising tools for clinical multiomics applications and prediction of chemotherapy and immunotherapy response and present benefits in terms of precision medicine and individualized treatment decision-making for pancreatic cancer patients.© 2023 The Authors.