As a type of programmed cell death, necroptosis is thought to play a dual role in tumorigenesis. However, a comprehensive assessment of necroptosis-related regulators across human cancers has not been reported. Therefore, in this study, we established a quantitative index to evaluate the necroptosis rate and determine its correlations with clinical prognosis, signaling pathways and molecular features, immune cell infiltration and regulation, immunotherapy, and chemotherapy sensitivity across cancers. Our results indicated that the necroptosis score can act as a favorable or risky prognostic factor in various cancer types. A gene set variation analysis suggested that necroptosis is significantly associated with immune- and inflammation-related signaling pathways, cell growth and apoptosis, and energy metabolism. Furthermore, necroptosis can affect the tumor microenvironment and immunity regulation, and the effect of necroptosis on immunity is different in different tumor types. There is crosstalk between components of necroptosis, pyroptosis, ferroptosis and autophagy pathways in multiple types of cancers. Finally, the necroptosis rate can be an indicator of immunotherapy effectiveness in multiple cancers and can affect the chemotherapy sensitivity of cancer cells. Our study presents a characterization of necroptosis across human cancers, highlights the potential necroptotic effects on immune regulation, and provides new insights into the development of individualized tumor treatments and clinical applications of immunotherapy.

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坏死性凋亡新指标的泛癌分析及其在人类癌症中的应用

作为一种程序性细胞死亡，坏死性凋亡被认为在肿瘤发生中发挥双重作用。然而，尚未报道对人类癌症中坏死性凋亡相关调节因子的综合评估。因此，在本研究中，我们建立了一个定量指标来评估坏死性凋亡率，并确定其与临床预后、信号通路和分子特征、免疫细胞浸润和调节、免疫治疗以及跨癌症化疗敏感性的相关性。我们的结果表明，坏死性凋亡评分可以作为各种癌症类型的有利或危险的预后因素。基因组变异分析表明，坏死性凋亡与免疫和炎症相关的信号通路、细胞生长和凋亡以及能量代谢显着相关。此外，坏死性凋亡可影响肿瘤微环境和免疫调节，不同肿瘤类型坏死性凋亡对免疫的影响不同。在多种类型的癌症中，坏死性凋亡、细胞焦亡、铁死亡和自噬途径的成分之间存在串扰。最后，坏死率可以作为多种癌症免疫治疗有效性的指标，并可以影响癌细胞的化疗敏感性。我们的研究展示了人类癌症中坏死性凋亡的特征，强调了坏死性凋亡对免疫调节的潜在影响，并为个体化肿瘤治疗的发展和免疫疗法的临床应用提供了新的见解。在多种类型的癌症中，坏死性凋亡、细胞焦亡、铁死亡和自噬途径的成分之间存在串扰。最后，坏死率可以作为多种癌症免疫治疗有效性的指标，并可以影响癌细胞的化疗敏感性。我们的研究展示了人类癌症中坏死性凋亡的特征，强调了坏死性凋亡对免疫调节的潜在影响，并为个体化肿瘤治疗的发展和免疫疗法的临床应用提供了新的见解。在多种类型的癌症中，坏死性凋亡、细胞焦亡、铁死亡和自噬途径的成分之间存在串扰。最后，坏死率可以作为多种癌症免疫治疗有效性的指标，并可以影响癌细胞的化疗敏感性。我们的研究展示了人类癌症中坏死性凋亡的特征，强调了坏死性凋亡对免疫调节的潜在影响，并为个体化肿瘤治疗的发展和免疫疗法的临床应用提供了新的见解。