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Abstract：
During the progression of renal cell carcinoma (RCC), tumor growth, metastasis and treatment response heterogeneity are regulated by both the tumor itself and the tumor microenvironment (TME). The aim of the present study was to investigate the role of the TME in RCC and construct a crosstalk network for clear cell RCC (ccRCC). An additional aim was to evaluate whether TNF receptor superfamily member 1A (TNFRSF1A) is a potential therapeutic target for ccRCC. Single-cell data analysis of RCC was performed using the GSE152938 dataset, focusing on key cellular components and their involvement in the ccRCC TME. Additionally, cell-cell communication was analyzed to elucidate the complex network of the ccRCC microenvironment. Analyses of data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases were performed to further mine the key TNF receptor genes, with a particular focus on the prediction and assessment of the cancer-associated features of TNFRSF1A. In addition, following the silencing of TNFRSF1A using small interfering RNA in the 786-O ccRCC cell line, a number of in vitro experiments were conducted to further investigate the cancer-promoting characteristics of TNFRSF1A. These included 5-ethynyl-2\'-deoxyuridine incorporation, Cell Counting Kit-8, colony formation, Transwell, cell cycle and apoptosis assays. The TNF signaling pathway was found to have a critical role in the development of ccRCC. Based on the specific crosstalk identified between TNF and TNFRSF1A, the communication of this signaling pathway within the TME was elucidated. The results of the cellular phenotype experiments indicated that TNFRSF1A promotes the proliferation, migration and invasion of ccRCC cells. Consequently, it is proposed that targeting TNFRSF1A may disrupt tumor progression and serve as a therapeutic strategy. In conclusion, by understanding the TME and identifying significant crosstalk within the TNF signaling pathway, the potential of TNFRSF1A as a therapeutic target is highlighted. This may facilitate an advance in precision medicine and improve the prognosis for patients with RCC.
摘要：
在肾细胞癌（RCC）的进展过程中，肿瘤生长，转移和治疗反应异质性受肿瘤本身和肿瘤微环境（TME）的调节。本研究的目的是研究TME在RCC中的作用，并构建透明细胞RCC（ccRCC）的串扰网络。另一个目的是评估TNF受体超家族成员1A(TNFRSF1A)是否是ccRCC的潜在治疗靶标。使用GSE152938数据集进行RCC的单细胞数据分析，重点关注关键细胞成分及其在ccRCCTME中的参与。此外,分析了ccRCC微环境的复杂网络。对来自癌症基因组图谱和临床蛋白质组学肿瘤分析联盟数据库的数据进行分析，以进一步挖掘关键的TNF受体基因，特别关注TNFRSF1A的癌症相关特征的预测和评估。此外,在786-OccRCC细胞系中使用小干扰RNA沉默TNFRSF1A之后，进行了大量体外实验以进一步研究TNFRSF1A的促癌特性.这些包括5-乙炔基-2'-脱氧尿苷掺入，细胞计数试剂盒-8，集落形成，Transwell,细胞周期和凋亡测定。发现TNF信号通路在ccRCC的发展中起关键作用。根据确定的TNF和TNFRSF1A之间的特定串扰，阐明了该信号通路在TME内的通讯.细胞表型实验结果表明TNFRSF1A促进细胞增殖，ccRCC细胞的迁移和侵袭。因此,有人提出靶向TNFRSF1A可能会干扰肿瘤进展并作为治疗策略.总之,通过了解TME并识别TNF信号通路内的显著串扰，强调了TNFRSF1A作为治疗靶标的潜力.这可能会促进精准医学的发展并改善RCC患者的预后。
