Department of Urology, Baoying People's Hospital, Xincheng Road, Baoying, Yangzhou, 225800, Jiangsu, China.
Department of Good Clinical Practice Office, Nanjing First Hospital, Nanjing Medical University, ChangLe Road 68, Qinhuai District, Nanjing, Jiangsu, China.
J Cancer Res Clin Oncol. 2024 May 27;150(5):278. doi: 10.1007/s00432-024-05761-y.
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.
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述。
通过综合算法构建了一个描述 ccRCC 中坏死性凋亡各方面的预后模型，并利用 E-MTAB-1980 数据集进行外部验证。通过利用多种算法探索免疫浸润评分。从 GSE171306 数据集获取单细胞 RNA 测序数据。采用实时定量 PCR（RT-qPCR）检测 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）和划痕愈合实验评估 769-P 和 786-O 细胞的增殖和转移变化。
坏死性凋亡相关特征（NRS）是一种区分患者免疫特征、肿瘤突变负担、免疫治疗反应和药物敏感性的指标。单细胞 RNA 测序分析显示 SLC25A37 在肿瘤细胞中明显富集。同时，RT-qPCR 显示 SLC25A37 在 ccRCC 组织和细胞系中均过表达。SLC25A37 敲低可通过 CCK8 和划痕愈合实验减轻 769-P 和 786-O 细胞的增殖和转移倾向。
NRS 在确定 ccRCC 患者的预后、肿瘤突变负担、免疫治疗反应、药物敏感性和免疫细胞浸润特征方面起着关键作用。SLC25A37 是免疫抑制微环境中的一个潜在靶点，为设计 ccRCC 的新型免疫治疗靶点提供了一个有前途的途径。
