Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Aging (Albany NY). 2023 Oct 20;15(20):11286-11297. doi: 10.18632/aging.205127.
Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted.
In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC.
Analysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients ( < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells.
STK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.
哺乳动物 STE20 样激酶 1（MST1/STK4/KRS2）是一种高度保守的丝氨酸/苏氨酸激酶，是 Hippo 信号通路的核心成员。已有研究报道 STK4 在各种肿瘤中发挥着重要作用，但尚未对其在透明细胞肾细胞癌（ccRCC）中的功能进行系统和全面的研究。
在本研究中，我们使用免疫组织化学（IHC）、蛋白质印迹（WB）、实时定量 PCR（qPCR）实验和生物信息学分析，全面分析 STK4 在 ccRCC 中的表达、预后价值和免疫浸润情况。
TCGA 数据库分析显示，ccRCC 患者的 STK4 基因表达水平取决于肿瘤分期、分级和远处淋巴转移。这一结果通过 IHC、WB 和 qPCR 实验得到了进一步证实。此外，我们使用接受者操作特征曲线（ROC 曲线）来阐明 STK4 在 ccRCC 患者中的诊断价值。根据 TIMER 数据库的结果，STK4 的高表达与肾癌（包括 ccRCC）患者的生存显著相关（<0.001），提示 STK4 是一种可靠的预后预测因子。随后，我们使用基因集富集分析（GSEA）来探讨 STK4 在 ccRCC 中的作用机制。我们发现 STK4 可能在免疫调节相互作用中发挥作用。接着，我们对 STK4 的免疫浸润进行了分析。结果表明，STK4 可能通过影响 NK 和 pDC 细胞的免疫浸润来调节 ccRCC 的发生发展。
STK4 可能是 ccRCC 的预后标志物，并可能有助于确定治疗 ccRCC 患者的新策略。
