高 TYROBP 和低 SOX6 可作为预测透明细胞肾细胞癌不良预后的生物标志物：一项初步研究。
Higher TYROBP and lower SOX6 as predictive biomarkers for poor prognosis of clear cell renal cell carcinoma: A pilot study.
机构信息
Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Department of plastic surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
出版信息
Medicine (Baltimore). 2022 Dec 23;101(51):e30658. doi: 10.1097/MD.0000000000030658.
BACKGROUND
Clear cell renal carcinoma (ccRCC) is the most common subtype of renal cancer, accounting for approximately 75% of all histological types of renal cancer, and is the leading cause of death from renal cancer. However, the molecular mechanism of tyrosine kinase binding protein (TYROBP) and sex-determining region Y Box-6 (SOX6) in the ccRCC was not precise.
METHODS
Bioinformatics analysis was performed to explore the hub role of TYROBP and SOX6 on the ccRCC. A total of 6 patients with clear cell renal cell carcinoma (ccRCC) were recruited. HE staining was performed to observe the pathology result of ccRCC. Immunohistochemistry and Immunofluorescence assay was made to detect the protein expression of TYROBP. Total RNA was extracted using TRIzol to examine the mRNA expression of TYROBP via the Real time quantitative polymerase chain reaction. The strong correlation between the expression of TYROBP and the survival time of ccRCC patients was performed by the BP neural network and support vector machine.
RESULTS
Compared with the control group, the expression of SOX6 was downregulated in the samples with ccRCC. However, the expression of TYROBP was higher in the samples with ccRCC than in the control group. Compared with the patients with high SOX6 expression, the patients with low SOX6 expression have a poor survival prognosis (HR=0.39, P < .05). However, the patients with high TYROBP expression have a shorter survival time than the patients with low TYROBP expression (HR=1.66, P < .05). The genes related with TYROBP and SOX6 are mainly enriched in the regulation of cell activation, leukocyte activation, negative regulation of cell activation, myeloid leukocyte activation, positive regulation of response to external stimulus, immune response-regulating signaling pathway. The interaction between TYROBP, SOX6, and kidney neoplasms was drawn, and the inference score of TYROBP and SOX6 on the kidney neoplasms was high.
CONCLUSION
In conclusion, TYROBP is highly expressed in renal clear cell carcinoma, and when this molecule is highly expressed, the survival prognosis of renal carcinoma is poor. TYROBP and SOX6 may be potential targets for diagnosing and treating renal clear cell carcinoma.
背景
透明细胞肾细胞癌（ccRCC）是最常见的肾癌亚型，约占所有肾癌组织学类型的 75%，是肾癌死亡的主要原因。然而，酪氨酸激酶结合蛋白（TYROBP）和性别决定区 Y 盒 6（SOX6）在 ccRCC 中的分子机制尚不清楚。
方法
通过生物信息学分析探讨 TYROBP 和 SOX6 在 ccRCC 中的核心作用。共招募 6 名透明细胞肾细胞癌（ccRCC）患者。行 HE 染色观察 ccRCC 的病理结果。采用免疫组织化学和免疫荧光法检测 TYROBP 蛋白的表达。采用 TRIzol 提取总 RNA，通过实时定量聚合酶链反应检测 TYROBP 的 mRNA 表达。采用 BP 神经网络和支持向量机分析 TYROBP 表达与 ccRCC 患者生存时间的强相关性。
结果
与对照组相比，ccRCC 样本中 SOX6 的表达下调，而 TYROBP 的表达高于对照组。与 SOX6 高表达的患者相比，SOX6 低表达的患者预后不良（HR=0.39，P<.05）。然而，TYROBP 高表达的患者生存时间短于 TYROBP 低表达的患者（HR=1.66，P<.05）。与 TYROBP 和 SOX6 相关的基因主要富集在细胞激活、白细胞激活、细胞激活的负调节、髓样白细胞激活、对外源性刺激的正向调节、免疫反应调节信号通路的调节。绘制了 TYROBP、SOX6 与肾脏肿瘤的相互作用图，TYROBP 和 SOX6 对肾脏肿瘤的推断评分较高。
结论
总之，TYROBP 在肾透明细胞癌中高表达，当该分子高表达时，肾癌的生存预后较差。TYROBP 和 SOX6 可能是诊断和治疗肾透明细胞癌的潜在靶点。
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