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Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor  PTTG1  was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of  PTTG1  had yet to be verified, and the mechanism of abnormal  PTTG1  expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of  PTTG1  expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of  PTTG1  in ESCC by combining the target genes of  PTTG1  (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and  PTTG1 -related genes, revealing the potential molecular mechanism of  PTTG1  in ESCC. In the present study,  PTTG1  protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall  PTTG1  expression was 1.17 (95% CI: 0.72–1.62,  P  < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83–0.89). By combining the target genes displayed by ChIP-seq of  PTTG1 , DEGs of ESCC, and  PTTG1 -related genes, it was observed that  PTTG1  may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein–protein interaction (PPI) network and combining ChIP-seq data, we obtained four  PTTG1  potential target genes,  SPTAN1 ,  SLC25A17 ,  IKBKB , and  ERH . The gene expression of  PTTG1  had a strong positive correlation with  SLC25A17  and  ERH , which suggested that  PTTG1  might positively regulate the expression of these two genes. In summary, the high expression of  PTTG1  may play an important role in the formation of ESCC. These roles may be completed by  PTTG1  regulating the downstream target genes  SLC25A17  and  ERH .

The Clinical Significance and Potential Molecular Mechanism of PTTG1 in Esophageal Squamous Cell Carcinoma