PANoptosis 是一种由 PANoptosome 调节的炎症性程序性细胞死亡。这种全凋亡具有细胞焦亡、细胞凋亡和坏死性凋亡的关键特征,但不能用这些细胞死亡模式中的任何一种来完全解释。这种细胞死亡机制的独特性质引起了人们的极大兴趣。然而,PANoptosis 相关特征在胃癌 (GC) 中的具体作用仍不确定。根据 PANoptosome 相关基因的表达情况,将患者分为不同的 PAN 亚型。我们进行了系统分析,以研究这些亚型之间预后和肿瘤微环境(TME)的差异。此外,我们还开发了一种风险评分,称为 PANoptosis 相关风险评分 (PANS),它是由与 PANoptosis 相关的基因构建的。我们综合分析了PANS与GC预后、TME、免疫治疗疗效和化疗药物敏感性之间的相关性。此外,我们还进行了体外实验来验证角蛋白 7 ( KRT7 ) 对 GC 的影响。我们确定了两种 PAN 亚型(PANcluster A 和 B)。 PANcluster A中PANoptosome基因高表达。PANcluster A具有预后良好、抗肿瘤淋巴细胞浸润丰富、对免疫治疗敏感等特点,属于免疫炎症型。同时,我们构建的PANS可以有效预测GC的预后和免疫效果。低PANS患者预后良好,具有肿瘤突变负荷(TMB)高、微卫星不稳定性(MSI)高、肿瘤纯度低、对免疫治疗敏感等特点。此外,PANS还可以识别不同化疗药物的合适人群。 最后,我们证实KRT7在GC中高表达。敲低KRT7的表达会显着削弱GC细胞的增殖和迁移能力。基于PANoptosis特征的模型有助于识别GC的TME特征,并能有效预测GC的预后和免疫效果。此外, KRT7的实验验证结果为抗肿瘤治疗提供了理论支持。
"点击查看英文标题和摘要"
PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer
PANoptosis is a form of inflammatory programmed cell death that is regulated by the PANoptosome. This PANoptosis possesses key characteristics of pyroptosis, apoptosis, and necroptosis, yet cannot be fully explained by any of these cell death modes. The unique nature of this cell death mechanism has garnered significant interest. However, the specific role of PANoptosis-associated features in gastric cancer (GC) is still uncertain. Patients were categorized into different PAN subtypes based on the expression of genes related to the PANoptosome. We conducted a systematic analysis to investigate the variations in prognosis and tumor microenvironment (TME) among these subtypes. Furthermore, we developed a risk score, called PANoptosis-related risk score (PANS), which is constructed from genes associated with the PANoptosis. We comprehensively analyzed the correlation between PANS and GC prognosis, TME, immunotherapy efficacy and chemotherapeutic drug sensitivity. Additionally, we performed in vitro experiments to validate the impact of Keratin 7 (KRT7) on GC. We identified two PAN subtypes (PANcluster A and B). PANoptosome genes were highly expressed in PANcluster A. PANcluster A has the characteristics of favorable prognosis, abundant infiltration of anti-tumor lymphocytes, and sensitivity to immunotherapy, thus it was categorized as an immune-inflammatory type. Meanwhile, our constructed PANS can effectively predict the prognosis and immune efficacy of GC. Patients with low PANS have a good prognosis, and have the characteristics of high tumor mutation load (TMB), high microsatellite instability (MSI), low tumor purity and sensitivity to immunotherapy. In addition, PANS can also identify suitable populations for different chemotherapy drugs. Finally, we confirmed that KRT7 is highly expressed in GC. Knocking down the expression of KRT7 significantly weakens the proliferation and migration abilities of GC cells. The models based on PANoptosis signature help to identify the TME features of GC and can effectively predict the prognosis and immune efficacy of GC. Furthermore, the experimental verification results of KRT7 provide theoretical support for anti-tumor treatment.