Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer.

Mengsi Yu,Lijuan Wang,Conghua Ning,Boke Zhang,Ning Feng,Zhaoxia Zhang,Changcheng Yang,Kainan Zhang,Li Xue,Zhaoyun Chen,Jing Li,Song Wang,Maria Irene Bellini

doi:10.1155/2021/8861766

Abstract

Objective SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. Materials and Methods The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. Results The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. Conclusions Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

Highlights

Pancreatic cancer is one of the most aggressive malignancies
To explore the potential roles of Sphingosine kinase 1 (SPHK1) and Hyaluronan synthases 2 (HAS2) in pancreatic cancer, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression of SPHK1 and HAS2
The results showed that the mRNA expression of SPHK1 and HAS2 was significantly higher in pancreatic cancer group (177 cases) than those of the healthy control (173 cases) (P < 0:05 and P < 0:05), respectively (Figure 1(a))

Summary

Introduction

Pancreatic cancer is one of the most aggressive malignancies. In China, the incidence of pancreatic cancer has increased 6fold in the past decades. The median survival time of pancreatic cancer patients is only 3-6 months, with a 5-year survival rate of less than 5% [1, 2]. Pancreatic cancer remains a poor prognostic cancer type and surgery is the only chance for cure. Pancreatic cancer is characterized by high invasiveness and early metastasis, lacking of specific symptoms in early stage [3]. A few patients are able to be cured surgically, due to the late diagnosis. There is no sensitive and specific biomarker to diagnose pancreatic cancer and predict the prognosis [4]

Methods

Results

Conclusion