Upregulated expression of PTTG1 is associated with progression of pancreatic cancer

Abstract

Background: Pancreatic cancer (PC) is an aggressive disease with a very poor prognosis. The insidious onset, rapid progression, and resistance to conventional therapies mark the imperious need for novel biomarkers and therapeutic targets. The pituitary tumor transforming gene 1 (PTTG1), implicated in tumorigenesis and cellular transformation, has been studied in various cancers, however, its role and mechanisms in PC remain to be elucidated for better understanding the disease pathology and in enhancing patient management strategies. Methods: The present study examined the PTTG1 messenger RNA (mRNA) expression levels and clinical significance through meta-analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was used to measure PTTG1 protein levels in PC and adjacent non-cancerous tissues. A correlation was observed between PTTG1 expression and some clinical characteristics based on the TCGA and IHC data. Univariate and multivariate Cox regressions were used to identify independent prognostic factors. Kaplan-Meier (KM) survival analysis was performed. The co-expressed genes of PTTG1 were determined by integrating online tools, and the enrichment analyses were performed to determine PTTG1-related pathways and hub co-expressed genes. Results: PTTG1 was highly expressed in PC tissues based on the TCGA, GEO, and IHC data. The combined standard mean difference (SMD) values of PTTG1 expression based on TCGA and GEO databases was 1.02 [95% confidence interval (CI): 0.74–1.30]. The area under the curve (AUC) based on the summary receiver operating characteristic (sROC) curve was 0.93 (95% CI: 0.90–0.95). PTTG1 overexpression was remarkably correlated with an inferior overall survival (OS). A total of 367 genes were identified as co-expressed genes of PTTG1 in PC and were mainly involved in the cell cycle pathway. The four identified core genes were CDK1, CCNA2, CDC20, and MAD2L1. Conclusions: The upregulated expression of PTTG1 plays an essential role in PC’s progression as a biomarker.