Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, 462020, India.
Centre for Advance Research, King George's Medical University, Lucknow, 226003, India.
Comput Biol Med. 2021 Feb;129:104141. doi: 10.1016/j.compbiomed.2020.104141. Epub 2020 Nov 26.
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, plays a crucial role in tumorigenesis. It mediates its function through S1P receptors. A few components of the S1P signaling pathway, such as sphingosine kinase 1 (SphK1) and S1P receptor 1 (S1PR1), have been shown to contribute to lung carcinogenesis. In the present study, using web-based computational tools, we assessed the prognostic roles of eight S1P metabolizing enzymes and five S1P receptors in non-small-cell lung cancer (NSCLC) patients. Except for SPHK1, low expression of S1P metabolizing enzymes was correlated with worse overall survival (OS) in NSCLC patients. Moreover, lower expression of lipid phosphate phosphatase-1 and - 3 (PLPP1 and PLPP3) was significantly associated with worse OS in lung adenocarcinoma (LUAD) and non-smoker NSCLC patients. Furthermore, the UALCAN database analysis showed that mRNA and protein expression of PLPP3 and S1PR1 are significantly down regulated in primary tumors due to hypermethylation of their respective promoters. Expression of PLPP3, S1PR1, and S1PR4 was positively correlated with tumor-infiltrating immune cells in NSCLC patients. These results indicate that S1P signaling genes play a critical prognostic role in LUAD patients. Therefore, this gene signature could be used to predict their prognosis more accurately.
鞘氨醇-1-磷酸（S1P）是一种生物活性鞘脂，在肿瘤发生中起着至关重要的作用。它通过 S1P 受体发挥其功能。S1P 信号通路的一些成分，如鞘氨醇激酶 1（SphK1）和 S1P 受体 1（S1PR1），已被证明有助于肺癌的发生。在本研究中，我们使用基于网络的计算工具，评估了八种 S1P 代谢酶和五种 S1P 受体在非小细胞肺癌（NSCLC）患者中的预后作用。除了 SphK1 之外，S1P 代谢酶的低表达与 NSCLC 患者的总生存期（OS）较差相关。此外，脂质磷酸酶-1 和 -3（PLPP1 和 PLPP3）的低表达与肺腺癌（LUAD）和非吸烟者 NSCLC 患者的 OS 较差显著相关。此外，UALCAN 数据库分析表明，由于其启动子的超甲基化，PLPP3 和 S1PR1 的 mRNA 和蛋白表达在原发性肿瘤中显著下调。PLPP3、S1PR1 和 S1PR4 的表达与 NSCLC 患者肿瘤浸润免疫细胞呈正相关。这些结果表明 S1P 信号基因在 LUAD 患者中具有重要的预后作用。因此，该基因特征可用于更准确地预测其预后。
