AUTHOR=Chen Shang-Wei , Zhou Hua-Fu , Zhang Han-Jie , He Rong-Quan , Huang Zhi-Guang , Dang Yi-Wu , Yang Xia , Liu Jun , Fu Zong-Wang , Mo Jun-Xian , Tang Zhong-Qing , Li Chang-Bo , Li Rong , Yang Li-Hua , Ma Jie , Yang Lin-Jie , Chen Gang 

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

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.583085

DOI=10.3389/fgene.2020.583085

ISSN=1664-8021

ABSTRACT=<p>Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor <italic>PTTG1</italic> 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 <italic>PTTG1</italic> had yet to be verified, and the mechanism of abnormal <italic>PTTG1</italic> expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of <italic>PTTG1</italic> 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 <italic>PTTG1</italic> in ESCC by combining the target genes of <italic>PTTG1</italic> (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and <italic>PTTG1</italic>-related genes, revealing the potential molecular mechanism of <italic>PTTG1</italic> in ESCC. In the present study, <italic>PTTG1</italic> 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 <italic>PTTG1</italic> expression was 1.17 (95% CI: 0.72–1.62, <italic>P</italic> &lt; 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 <italic>PTTG1</italic>, DEGs of ESCC, and <italic>PTTG1</italic>-related genes, it was observed that <italic>PTTG1</italic> 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 <italic>PTTG1</italic> potential target genes, <italic>SPTAN1</italic>, <italic>SLC25A17</italic>, <italic>IKBKB</italic>, and <italic>ERH</italic>. The gene expression of <italic>PTTG1</italic> had a strong positive correlation with <italic>SLC25A17</italic> and <italic>ERH</italic>, which suggested that <italic>PTTG1</italic> might positively regulate the expression of these two genes. In summary, the high expression of <italic>PTTG1</italic> may play an important role in the formation of ESCC. These roles may be completed by <italic>PTTG1</italic> regulating the downstream target genes <italic>SLC25A17</italic> and <italic>ERH</italic>.</p>