Abstract
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.
Highlights
Esophageal cancer is the sixth leading cause of cancer-related deaths in the world and the eighth most common cancer globally; esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide (Arnal et al, 2015)
IHC staining of tissue chips showed that the PTTG1 protein expression level in ESCC tissues was significantly higher than in non-cancerous tissues (10.410 ± 1.880 vs. 7.410 ± 2.153, P < 0.0001; area under curve (AUC) = 0.8405, P < 0.0001) (Figure 1)
In order to confirm the high expression of PTTG1 in ESCC tissues, we collected ESCC tissues and their matched non-cancer tissues from eight clinical patients with ESCC and obtained in-house RNA-seq data of these samples
Summary
Esophageal cancer is the sixth leading cause of cancer-related deaths in the world and the eighth most common cancer globally; esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide (Arnal et al, 2015). Despite the improved management and treatment of ESCC patients, the overall 5-year survival rate (10%) and 5year survival rate following resection (15–40%) have remained low (Huang and Yu, 2018). The poor prognosis and rising morbidity of ESCC highlights the importance of improving detection methods, which is essential before treatment. As early clinical symptoms are not obvious, many ESCC patients are not diagnosed until the clinical symptoms appear in the late stage. In order to improve the prognosis of patients after surgery, patients were often treated with surgery combined with radiotherapy and chemotherapy, but this has not significantly increased the survival rate of ESCC patients. Since we have failed to fully understand the mechanism of the occurrence and development of ESCC, it is necessary and meaningful to explore its potential molecular mechanism to identify new prognostic biomarkers and potential ESCC therapeutic targets
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