SGPP1 as a tumor suppressor in esophageal squamous cell carcinoma: Potential molecular mechanisms involving UGT1A9/UGT2B28 and clinical prognostic significance.
TL;DR
SGPP1 functions as a tumor suppressor gene in ESCC and may inhibit tumor progression by regulating UGT1A9/UGT2B28‑mediated metabolic pathways and serve as a prognostic biomarker and a potential therapeutic target in ESCC.
Abstract
The present study aimed to characterize the expression pattern and biological function of sphingosine‑1‑phosphate phosphatase 1 (SGPP1) in esophageal squamous cell carcinoma (ESCC), investigate its potential molecular regulatory mechanisms, and evaluate its clinical value as a prognostic biomarker and therapeutic target. SGPP1 expression in ESCC cell lines was assessed by reverse transcription‑quantitative PCR and western blotting. Models of SGPP1 overexpression in KYSE150 cells and SGPP1 knockdown in ECA109 cells were established. 5‑Ethynyl‑2'‑deoxyuridine, Cell Counting Kit‑8, colony formation, terminal deoxynucleotidyl transferase dUTP nick‑end labeling, wound healing and Transwell assays were performed to systematically analyze the effects of SGPP1 on ESCC cell proliferation, apoptosis, migration and invasion. The Cancer Genome Atlas‑ESCC data were integrated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis and UpSet plotting to identify key downstream pathways and candidate target genes. SGPP1 protein expression was evaluated by immunohistochemistry in tumor tissues from 68 patients with ESCC, and Cox regression analysis was used to assess its association with patient prognosis. The results demonstrated that SGPP1 expression varied markedly among ESCC cell lines, with low expression in KYSE150 cells and high expression in ECA109 cells. SGPP1 overexpression significantly inhibited ESCC cell proliferation, migration and invasion, and increased apoptosis‑associated DNA fragmentation, whereas SGPP1 knockdown produced the opposite effects. Mechanistically, the data suggested that SGPP1 modulates extracellular matrix remodeling and xenobiotic metabolism, potentially through negative regulation of UGT1A9 and UGT2B28 expression. Clinically, low SGPP1 expression was an independent risk factor for poor prognosis in patients with ESCC (HR=6.016, 95% CI: 3.143‑11.513, P<0.001), and the overall survival was significantly longer in the high‑expression group than in the low‑expression group (P<0.001). In conclusion, SGPP1 functions as a tumor suppressor gene in ESCC and may inhibit tumor progression by regulating UGT1A9/UGT2B28‑mediated metabolic pathways. SGPP1 may therefore serve as a prognostic biomarker and a potential therapeutic target in ESCC.