Overexpression of SPHK1 associated with targeted therapy resistance in predicting poor prognosis in renal cell carcinoma.
Overexpression of SPHK1 associated with targeted therapy resistance in predicting poor prognosis in renal cell carcinoma.
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DOI：
10.21037/tcr-22-417
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发表时间：
2023-03-31
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
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作者：
鞘氨醇激酶1（SPHK 1）是催化鞘氨醇磷酸化的关键酶。最近的研究报道SPHK 1通过诱导靶向治疗耐药与肾细胞癌（RCC）进展相关。然而，SPHK 1在接受靶向治疗的RCC中的表达及其临床意义尚未阐明。本研究探讨SPHK 1在靶向治疗后肾细胞癌组织中的表达，SPHK 1与肾细胞癌临床病理参数的相关性，以及SPHK 1对肾细胞癌患者预后的影响。对接受和未接受靶向治疗的肾细胞癌进行差异基因表达分析。分析SPHK 1表达与肾癌临床病理参数的关系。进行基因集富集分析（GSEA）以阐明SPHK 1与靶向治疗耐药性相关的潜在作用。SPHK 1作为肾细胞癌诊断标志物的价值也进行了评估。采用Kaplan-Meier法分析SPHK 1表达与肾癌患者生存率的相关性。SPHK 1在经靶向治疗的肾细胞癌中表达显著增高。SPHK 1表达与肾癌进展相关的临床病理参数密切相关。因此，SPHK 1的升高可以有效地诊断RCC，并区分晚期和高病理分级的RCC。SPHK 1通过激活靶向药物治疗或未治疗的RCC中的Wnt、Hedgehog或Notch信号通路与RCC细胞的干性相关。一个大的RCC样本队列的生存分析表明SPHK 1的过表达与RCC患者的总体和无病生存呈负相关。我们的研究表明，SPHK 1与靶向治疗耐药相关，可以作为一个潜在的预后标志物和一个有价值的生物标志物的反应，在肾细胞癌血管生成剂。
Sphingosine kinase 1 (SPHK1) is a key enzyme that catalyzes the phosphorylation of sphingosine. Recent studies reported SPHK1 to be associated with renal cell carcinoma (RCC) progression by inducing targeted therapy resistance. However, the expression and the clinical significance of SPHK1 on RCC in those having received targeted therapy have not been elucidated. The present study explored the expression of SPHK1 in RCC tissues from targeted therapy recipients, the correlation of SPHK1 with clinicopathological parameters, and the effect of SPHK1 on RCC patient prognosis. Differential gene expression analysis of RCC treated with and without targeted therapy was performed. The correlations of SPHK1 expression with clinical parameters of RCC were examined. Gene set enrichment analysis (GSEA) was performed to clarify the potential role of SPHK1 associated with targeted therapy resistance. The value of SPHK1 as a diagnostic marker for RCC was also evaluated. The Kaplan-Meier method was applied to analyze the correlation between SPHK1 expression and patient survival rate by using the clinical data from patients with RCC. Significant overexpression of SPHK1 was detected in RCC treated with targeted therapy. SPHK1 expression was closely correlated with RCC progression-related clinicopathological parameters. Therefore, elevated SPHK1 could effectively diagnose RCC and distinguish RCC with an advanced clinical stage and a high pathological grade. SPHK1 was associated with the stemness of RCC cells via the activation of the Wnt, Hedgehog, or Notch signaling pathways in targeted drug-treated or untreated RCC. Survival analysis of a large cohort of RCC samples indicated overexpression of SPHK1 to be inversely correlated with the overall and disease-free survival of patients with RCC. Our study indicated that SPHK1 associated with targeted therapy resistance could serve as a potential prognostic marker and a valuable biomarker of response to angiogenic agents in RCC.
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影响因子：
4.7
作者：
Li, Run-Ze;Wang, Xuan-Run;Wang, Jian;Xie, Chun;Wang, Xing-Xia;Pan, Hu-Dan;Meng, Wei-Yu;Liang, Tu-Liang;Li, Jia-Xin;Yan, Pei-Yu;Wu, Qi-Biao;Liu, Liang;Yao, Xiao-Jun;Leung, Elaine Lai-Han
通讯作者：
Leung, Elaine Lai-Han
DOI：
10.1158/1078-0432.ccr-14-2031
发表时间：
2015-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Zhang L;Wang X;Bullock AJ;Callea M;Shah H;Song J;Moreno K;Visentin B;Deutschman D;Alsop DC;Atkins MB;Mier JW;Signoretti S;Bhasin M;Sabbadini RA;Bhatt RS
通讯作者：
Bhatt RS
影响因子：
--
作者：
Pastore AL;Palleschi G;Silvestri L;Moschese D;Ricci S;Petrozza V;Carbone A;Di Carlo A
通讯作者：
Di Carlo A
影响因子：
5.6
作者：
Bao, Ji-Ming;Dang, Qiang;Tan, Wan-Long
通讯作者：
Tan, Wan-Long
靶向癌症干细胞中的信号通路进行癌症治疗
影响因子：
4.3
作者：
Koury J;Zhong L;Hao J
通讯作者：
Hao J