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Abstract：
BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most prevalent type of renal cell carcinoma (RCC), with a high incidence and mortality rate. There is a lack of sensitive biomarkers. Therefore, the discovery of accurate biomarkers for KIRC patients is critical to improve prognosis.
METHODS: We determined hub genes and their associated pathways involved in the pathogenesis of KIRC from the GSE66272 dataset consisting of KIRC (n = 26) and corresponding control (n = 26) samples and later validated the expression and methylation level of the identified hub genes on The Cancer Genomic Atlas (TCGA) datasets and Human RCC 786-O and normal HK-2 cell lines through RNA sequencing (RNA-seq), Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and targeted bisulfite sequencing (bisulfite-seq) analyses.
RESULTS: The identified up-regulated four hub genes include TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), PTPRC (Protein tyrosine phosphatase, receptor type, C), LCP2 (Lymphocyte cytosolic protein 2), and ITGB2 (Integrin Subunit Beta 2). Moreover, the higher expression of TYROBP, PTPRC, LCP2, and ITGB2 in KIRC patients insignificantly correlates with a poor prognosis in KIRC patients. In addition, hub genes were involved in the \"Fc epsilon RI signaling pathway, asthma, natural cell killer mediated cytotoxicity, T cell receptor signaling pathway, primary immunodeficiency, Fc gamma R-mediated phagocytosis, malaria, leukocyte transendothelial migration, and legionellosis\" pathways and associated with the infiltration level of CD8+ T, CD4+ T, and macrophage cells.
CONCLUSIONS: Our integrated in silico and in vitro analysis identified important hub genes (TYROBP, PTPRC, LCP2, and ITGB2) involved in the pathogenesis of KIRC as possible diagnostic biomarkers.
METHODS: We determined hub genes and their associated pathways involved in the pathogenesis of KIRC from the GSE66272 dataset consisting of KIRC (n = 26) and corresponding control (n = 26) samples and later validated the expression and methylation level of the identified hub genes on The Cancer Genomic Atlas (TCGA) datasets and Human RCC 786-O and normal HK-2 cell lines through RNA sequencing (RNA-seq), Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and targeted bisulfite sequencing (bisulfite-seq) analyses.
RESULTS: The identified up-regulated four hub genes include TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), PTPRC (Protein tyrosine phosphatase, receptor type, C), LCP2 (Lymphocyte cytosolic protein 2), and ITGB2 (Integrin Subunit Beta 2). Moreover, the higher expression of TYROBP, PTPRC, LCP2, and ITGB2 in KIRC patients insignificantly correlates with a poor prognosis in KIRC patients. In addition, hub genes were involved in the \"Fc epsilon RI signaling pathway, asthma, natural cell killer mediated cytotoxicity, T cell receptor signaling pathway, primary immunodeficiency, Fc gamma R-mediated phagocytosis, malaria, leukocyte transendothelial migration, and legionellosis\" pathways and associated with the infiltration level of CD8+ T, CD4+ T, and macrophage cells.
CONCLUSIONS: Our integrated in silico and in vitro analysis identified important hub genes (TYROBP, PTPRC, LCP2, and ITGB2) involved in the pathogenesis of KIRC as possible diagnostic biomarkers.
摘要：
背景：肾透明细胞癌（KIRC）是最常见的肾细胞癌（RCC）类型，具有很高的发病率和死亡率。缺乏敏感的生物标志物。因此,发现KIRC患者的准确生物标志物对改善预后至关重要.
方法：我们从由KIRC（n=26）和相应对照（n=26）样品组成的GSE66272数据集确定了与KIRC发病机理有关的hub基因及其相关途径，随后通过RNA测序验证了在癌症基因组图谱（TCGA）数据集和人类RCC786-O和正常HK-q细胞系上鉴定的hub基因的表达和甲基化水平逆转录-定量聚合酶链反应(RT-qPCR),和靶向亚硫酸氢盐测序(亚硫酸氢盐-seq)分析。
结果：确定的上调的四个hub基因包括TYROBP（跨膜免疫信号接头TYROBP），PTPRC（蛋白酪氨酸磷酸酶，受体类型,C),LCP2（淋巴细胞胞浆蛋白2），和ITGB2(整合素亚基β2)。此外，TYROBP的表达越高，PTPRC,KIRC患者的LCP2和ITGB2与KIRC患者的不良预后无关。此外,hub基因参与“FcεRI信号通路，哮喘,自然细胞杀伤介导的细胞毒性，T细胞受体信号通路,原发性免疫缺陷,FcγR介导的吞噬作用，疟疾,白细胞跨内皮迁移，和军团菌病的途径，并与CD8+T的浸润水平有关，CD4+T,和巨噬细胞。
结论：我们的计算机集成和体外分析鉴定了重要的枢纽基因（TYROBP，PTPRC,LCP2和ITGB2）参与KIRC的发病机理，可能是诊断性生物标志物。
方法：我们从由KIRC（n=26）和相应对照（n=26）样品组成的GSE66272数据集确定了与KIRC发病机理有关的hub基因及其相关途径，随后通过RNA测序验证了在癌症基因组图谱（TCGA）数据集和人类RCC786-O和正常HK-q细胞系上鉴定的hub基因的表达和甲基化水平逆转录-定量聚合酶链反应(RT-qPCR),和靶向亚硫酸氢盐测序(亚硫酸氢盐-seq)分析。
结果：确定的上调的四个hub基因包括TYROBP（跨膜免疫信号接头TYROBP），PTPRC（蛋白酪氨酸磷酸酶，受体类型,C),LCP2（淋巴细胞胞浆蛋白2），和ITGB2(整合素亚基β2)。此外，TYROBP的表达越高，PTPRC,KIRC患者的LCP2和ITGB2与KIRC患者的不良预后无关。此外,hub基因参与“FcεRI信号通路，哮喘,自然细胞杀伤介导的细胞毒性，T细胞受体信号通路,原发性免疫缺陷,FcγR介导的吞噬作用，疟疾,白细胞跨内皮迁移，和军团菌病的途径，并与CD8+T的浸润水平有关，CD4+T,和巨噬细胞。
结论：我们的计算机集成和体外分析鉴定了重要的枢纽基因（TYROBP，PTPRC,LCP2和ITGB2）参与KIRC的发病机理，可能是诊断性生物标志物。
