Identification and validation of LDHA and SLC16A1 for predicting prognosis and diagnosis in lower-grade glioma

鉴定和验证LDHA和SLC16A1在预测低级别胶质瘤预后和诊断中的作用

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Abstract

PURPOSE: This study aimed to analyze the prognostic and diagnostic value of Lactate dehydrogenase A (LDHA) and solute carrier family 16 member 1 (SLC16A1) in low-grade gliomas (LGG). METHODS: Gene expression datasets for LGG were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. The prognostic value of LDHA and SLC16A1 in LGG was analyzed using the survival package. Receiver operating characteristic (ROC) curves were drawn to evaluate the ability of the model to distinguish between patients with LGG and controls. Gene set enrichment analysis (GSEA) of single gene was utilized to explore the potential biological function of the two genes. The protein levels of LDHA and SLC16A1 were analyzed using the Human Protein Atlas database. LDHA and SLC16A1 expression was verified using real-time reverse transcription polymerase chain reaction. Finally, the effects of low SLC16A1 expression on the proliferation, migration, and invasion of LGG cells were investigated using CCK-8 and Transwell assays. RESULTS: LDHA was downregulated, and SLC16A1 was upregulated in LGG tissues compared to normal tissues in TCGA dataset. Kaplan-Meier (K-M) survival and ROC curves revealed that these two genes have potential prognostic and diagnostic performances. LDHA positively correlated with SLC16A1 in TCGA and CGGA cohorts. GSEA demonstrated that LDHA is involved in the chemokine and NOD-like receptor signaling pathways, whereas SLC16A1 is involved in the JAK-STAT and NOD-like receptor signaling pathways. Immunohistochemical profiles of LDHA and SLC16A1 were consistent with their mRNA expression levels. SLC16A1 overexpression and downregulation of LDHA have been validated in glioma cell lines. Additionally, low SLC16A1 expression inhibited the proliferation, migration, and invasion of glioma cells. CONCLUSION: LDHA and SLC16A1 have potential prognostic and diagnostic values for LGG. Therefore, SLC16A1 may serve as a potential biomarker for the diagnosis and treatment of LGG.

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