The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer.

Junjie Hang,Lixia Wu,Siyuan Zhou,Lina Zhu,Xin Yuan,Ruohan Yin,Steven Yuk-Fai Lau

doi:10.1042/bsr20203282

Abstract

Compelling evidence suggests that phosphoprotein phosphatases (PPPs) are involved in a large spectrum of physiological and pathological processes, but little is known about their roles in pancreatic cancer. We investigated the expression level, prognostic value, and potential function of PPPs with data from Oncomine, GEPIA, THPA, and TCGA databases and an independent cohort of patients with pancreatic cancer. Among all the PPP catalytic subunits (PPPcs), the transcription levels of PPP1CA, PPP1CB, PPP3CA, PPP3CB, and PPP4C were higher in pancreatic cancer than in normal pancreas (P<0.01, fold change > 2). Kaplan–Meier analysis showed that high transcription levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, and PPP4C correlated with poorer survival. In contrast, patients with high levels of PPP3CB, PPP3CC, PPP5C, PPP6C, and PPEF2 had much better prognoses. Data from THPA and patients with pancreatic cancer enrolled in our hospital also confirmed the prognostic value of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, and PPP6C at the protein level. In addition, the Pearson Chi-square test showed that PPP3CB level was significantly correlated with T and N stages. GO and KEGG analyses showed that the genes and pathways related to the pathogenesis and progression of pancreatic cancer were greatly affected by alterations in PPPcs. Results of the present study suggest that PPP1CA, PPP1CB, PPP2CA, PPP2CB, and PPP3CA have deleterious effects but PPP3CB, PPP5C, and PPP6C have beneficial effects on pancreatic cancer.

Highlights

Pancreatic cancer is a highly lethal malignancy, with almost as many cancer-related deaths (n=432,242) as cases (n=459,000) worldwide [1]
We found that the mRNA expression levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, PPP4C, PPP5C, and PPP6C were higher in pancreatic adenocarcinoma than in normal tissues
Compelling evidence suggests that PPP catalytic subunits (PPPcs), a family of genes encoding the catalytic subunits of phosphoprotein phosphatase (PPP), are involved in a variety of physiological and pathological process, but little is known about PPPcs’ roles in pancreatic cancer

Summary

Introduction

Pancreatic cancer is a highly lethal malignancy, with almost as many cancer-related deaths (n=432,242) as cases (n=459,000) worldwide [1]. In China, there were an estimated 90,100 new cases and 79,400 deaths as a result of pancreatic cancer in 2015 [2]. Because of limited progress in diagnostic methods and effective therapeutic interventions, the prognosis for patients with pancreatic cancer remains dismal [3,4]. There is an urgent need to identify valuable biomarkers and promising therapeutic targets to improve the current diagnostic and treatment strategy for pancreatic cancer [6]. The PPP family consists of conserved catalytic subunits, including PPP1C to PPP7C ( known as PPEF), which diversify their biological functions by associating with different noncatalytic subunits [9]. The PPP catalytic subunits (PPPcs) have 13 different isoforms: PPP1CA, PPP1CB, PPP1CC, PPP2CA, PPP2CB, PPP3CA, PPP3CB, PPP3CC, PPP4C, PPP5C, PPP6C, PPEF1, and PPEF2 (Supplementary Table S1); even in the same PPPcs, different isoforms boast differential biochemical and regulatory properties [10]

Methods

Results

Conclusion