Prognostic role of lipid phosphate phosphatases in non-smoker, lung adenocarcinoma patients

• Published in: Computers in biology and medicine Vol. 129; p. 104141
• Main Authors: Nema, Rajeev, Shrivastava, Ashutosh, Kumar, Ashok
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.02.2021; Elsevier Limited
• Subjects: Adenocarcinoma; Biomarkers; Cancer therapies; Carcinogenesis; Carcinogens; Computer applications; Datasets; DNA methylation; Enzymes; Gene expression; Genomics; Immune system; Kinases; KM Plotter; Lipid phosphate phosphatase; Lipids; Lung cancer; Medical prognosis; Metabolism; Metabolites; mRNA; Non-small cell lung cancer; Non-small cell lung carcinoma; Phosphatase; Protein expression; Proteins; Receptor mechanisms; Receptors; Signal transduction; Signaling; Small cell lung carcinoma; Smoking; Software; Sphingosine 1-phosphate; Sphingosine kinase; Survival analysis; Tumor-infiltrating immune cells; Tumor-infiltrating lymphocytes; Tumorigenesis; Tumors; UALCAN database; Tumor-infiltrating immune cells; UALCAN database; KM Plotter; Lipid phosphate phosphatase; Sphingosine-1-phosphate; Non-small cell lung cancer
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2020.104141

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. •We demonstrate the prognostic value of S1P-signaling genes in NSCLC.•PLPP1, PLPP3 and S1PR1 exhibit prognostic value in the lung adenocarcinoma patients.•Expression of PLPP3 and S1PR1 is downregulated in the primary NSCLC tumors.•Expression of PLPP3 and S1PR1 correlates with infiltration of immune cells in NSCLC.•PLPP1, PLPP3, S1PR1 and ENPP2 show high prognostic value in multivariate analysis.