Lu Si-Yuan, Hua Jie, Liu Jiang, Wei Miao-Yan, Liang Chen, Meng Qing-Cai, Zhang Bo, Yu Xian-Jun, Wang Wei, Xu Jin, Shi Si
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Comput Struct Biotechnol J. 2023 Mar 23;21:2419-2433. doi: 10.1016/j.csbj.2023.03.037. eCollection 2023.
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.
越来越多的证据表明坏死性凋亡与胰腺癌之间存在潜在关联，坏死性凋亡、免疫浸润与胰腺癌微环境之间的关系也日益受到关注。然而，基于坏死性凋亡和免疫相结合的二维表型和预后评估系统尚未得到探索。在我们目前的研究中，我们探索了坏死性凋亡相关分子的泛癌基因组特征，确定了坏死性凋亡相关分子的突变谱、表达谱以及表达水平与甲基化/拷贝数变异水平之间的相关性。我们在胰腺癌中确定了不同的坏死性凋亡和免疫状态，高坏死性凋亡表型和高免疫表型均显示出比低坏死性凋亡表型和低免疫表型更好的预后。我们构建的二维表型对胰腺癌的预后、炎症和免疫微环境具有理想的判别效果。“高坏死性凋亡和高免疫（HNHI）”组表现出最佳预后和最高比例的浸润免疫细胞。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。我们的研究还表明，SLC2A1与坏死性凋亡和免疫均相关，并且在胰腺癌中作为一种潜在的癌基因发挥作用。总之，我们开发的二维表型和NI评分是临床多组学应用以及预测化疗和免疫治疗反应的有前景的工具，在胰腺癌患者的精准医学和个体化治疗决策方面具有优势。
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