The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. We primarily investigated the underlying mechanisms of OGT in SCLC. Herein, based on the analyses from pan-cancer to SCLC, OGT demonstrated conspicuous clinical significance. OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC.
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