NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma.

NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma.
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NCKAP1 是一种抑制透明细胞肾细胞癌细胞生长的预后生物标志物。

DOI:
10.3389/fgene.2022.764957
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发表时间:
2022
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学3区
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背景:肾透明细胞癌是最常见的肾癌类型。NCK相关蛋白1(NCKAP1)与多种肿瘤类型的预后不良和肿瘤进展有关,但NCKAP1在肾细胞癌中的作用和预后价值尚不清楚。方法:利用Ualcan数据库,分析NCKAP1在肾细胞癌中的表达与临床特征的相关性。在一组慢性肾细胞癌患者中,NCKAP1的免疫组织化学染色证实了这些数据。我们通过GEPIA2生存分析评估NCKAP1的预后价值。利用NCKAP1过表达的ACHN细胞株在体外和体内检测NCKAP1的功能。LinkedOmics和GSCALite数据库被用来研究和识别潜在的NCKAP1靶向药物,这些药物可能在治疗ccRCC中发挥作用。并评价NCKAP1的表达对免疫渗透的影响。结果:NCKAP1在肾细胞癌中表达明显下调,并与晚期临床病理特征和预后不良有关。NCKAP1在ACHN细胞中的过表达在体外降低了细胞的增殖、侵袭和迁移能力,并抑制了体内肿瘤的生长。根据LinkedOmics、GSCALite和Timer数据库,NCKAP1和相关基因主要在核糖体信号转导、氧化磷酸化、转化生长因子-β和EMT相关信号通路中发挥作用。NCKAP1与慢性肾细胞癌的免疫细胞类型、生物标记物和免疫检查点呈正相关。结论:NCKAP1在肾细胞癌中可能发挥重要的肿瘤抑制作用,是一个潜在的有用的预后生物标志物。
Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. Nck-associated protein 1 (NCKAP1) is associated with poor prognosis and tumor progression in several cancer types, but the function and prognostic value of NCKAP1 in ccRCC remain poorly understood. Methods: Using the Ualcan database, we evaluated the correlation between NCKAP1 expression and clinical features of ccRCC. These data were validated by immunohistochemical staining for NCKAP1 in a cohort of ccRCC patients. We assessed the prognostic value of NCKAP1 using GEPIA2 survival analysis. NCKAP1 function was characterized in vitro and in vivo using NCKAP1-overexpression ACHN cell lines. The LinkedOmics and GSCALite databases were used to investigate identify potential NCKAP1-targeted medicines that may play a role in the treatment of ccRCC. The impact of NCKAP1 expression on immune infiltration was also evaluated. Results: NCKAP1 was significantly downregulated in ccRCC and correlated with advanced clinicopathological features and poor prognosis. Overexpression of NCKAP1 in ACHN cells reduced proliferation, invasion and migration capacity in vitro and inhibited tumor growth in vivo. According to the LinkedOmics, GSCALite and TIMER databases, NCKAP1 and related genes function primarily in ribosomal signaling, oxidative phosphorylation, TGF-β, and EMT-related signaling pathways. NCKAP1 was also shown to positively correlate with immune cell types, biomarkers, and immune checkpoints in ccRCCs. Conclusions: NCKAP1 may play a vital tumor-suppressive role in ccRCC and is potentially a useful prognostic biomarker.