透明细胞肾细胞癌中 NETosis 相关预后模型的预后影响和免疫治疗意义。
Prognostic impact and immunotherapeutic implications of NETosis-related prognostic model in clear cell renal cell carcinoma.
发表日期:2024 May 27
作者:
Xingjun Mao, Wen Huang, Qing Xue, Xiaolei Zhang
来源:
Cell Death & Disease
摘要:
坏死性凋亡对透明细胞肾细胞癌 (ccRCC) 预后的影响仍未得到充分阐明。采用算法概要构建了描述 ccRCC 坏死性凋亡各个方面的预后模型。使用 E-MTAB-1980 数据集进行外部验证。通过利用多种算法来探索免疫渗透分数。单细胞 RNA 测序数据来自 GSE171306 数据集。采用实时定量 PCR (RT-qPCR) 来检查 SLC25A37 在癌症和癌旁组织以及不同细胞系中的差异表达。通过细胞计数试剂盒 8 (CCK8) 和伤口愈合检测完成对 769-P 和 786-O 细胞增殖和转移变化的评估。坏死性凋亡相关特征 (NRS) 作为一种辨别指标出现,描绘了患者的免疫属性、肿瘤突变负荷、免疫治疗反应和药物敏感性。单细胞 RNA 测序分析揭示了肿瘤细胞中 SLC25A37 的显着富集。同时,RT-qPCR 揭示了 SLC25A37 在 ccRCC 组织和细胞系中的过度表达。 CCK8 和伤口愈合试验证明,SLC25A37 敲低可减轻 769-P 和 786-O 细胞的增殖和转移倾向。NRS 在确定预后、肿瘤突变负担、免疫治疗反应、药物敏感性和免疫方面发挥着关键作用。 ccRCC 患者的细胞浸润特征。 SLC25A37 成为免疫抑制微环境中的公认参与者,从而为 ccRCC 创新免疫治疗靶点的设计提供了前瞻性途径。© 2024。作者。
The ramifications of necroptosis on the prognostication of clear cell renal cell carcinoma (ccRCC) remain inadequately expounded.A prognostic model delineating the facets of necroptosis in ccRCC was constructed, employing a compendium of algorithms. External validation was effectuated using the E-MTAB-1980 dataset. The exploration of immune infiltration scores was undertaken through the exploitation of multiple algorithms. Single-cell RNA sequencing data were procured from the GSE171306 dataset. Real-time quantitative PCR (RT-qPCR) was engaged to scrutinize the differential expression of SLC25A37 across cancer and paracancer tissues, as well as diverse cell lines. Assessments of proliferative and metastatic alterations in 769-P and 786-O cells were accomplished through Cell Counting Kit-8 (CCK8) and wound healing assays.The necroptosis-related signature (NRS) emerges as a discerning metric, delineating patients' immune attributes, tumor mutation burden, immunotherapy response, and drug susceptibility. Single-cell RNA sequencing analysis unveils the marked enrichment of SLC25A37 in tumor cells. Concurrently, RT-qPCR discloses the overexpression of SLC25A37 in both ccRCC tissues and cell lines. SLC25A37 knockdown mitigates the proliferative and metastatic propensities of 769-P and 786-O cells, as evidenced by CCK8 and wound healing assays.The NRS assumes a pivotal role in ascertaining the prognosis, tumor mutation burden, immunotherapy response, drug susceptibility, and immune cell infiltration features of ccRCC patients. SLC25A37 emerges as a putative player in immunosuppressive microenvironments, thereby providing a prospective avenue for the design of innovative immunotherapeutic targets for ccRCC.© 2024. The Author(s).