Prognostic significance of CIP2A expression in solid tumors: A meta-analysis.

Min Tang,Min Tang,Min Tang,Min Tang,Jiao-Feng Shen,Jiao-Feng Shen,Xi-Xi Cui,Li-Na Zhou,Li-Na Zhou,Li-Na Zhou,Li-Na Zhou,Ping Zeng,Ping Zeng,Min-Bin Chen,Min-Bin Chen,Ye Tian,Ye Tian,Ping Li,Ping Li,Ping Li,Ping Li,Hiromu Suzuki

doi:10.1371/journal.pone.0199675

Abstract

CIP2A, cancerous inhibitor of protein phosphatase 2A, was initially recognized as an oncoprotein. Recently several studies revealed that CIP2A could function as a prognosis biomarker, however, the result remained not comprehensive, partly due to small number of patients included individually. Here we carried out a meta-analysis of published studies to assess the prognostic significance of CIP2A in solid tumors. All eligible studies were identified through searching PubMed, Embase and Web of Science database. In this meta-analysis, 22 studies involving 4,579 participants were included, and we verified that CIP2A over-expression was significantly related with poor overall survival (pooled HR = 1.844, 95% CI = 1.528–2.225, P<0.001) and short disease free survival (pooled HR = 1.808, 95% CI = 1.591–2.055, P<0.001) in solid tumors. Additionally, subgroup analysis suggested that the trend of a poor overall survival with an increased CIP2A expression was present in East-Asian and European patients, as well as in lung cancer and colorectal cancer. To sum up, CIP2A over-expression was associated with poor survival in human solid tumors and might be a predictive factor of poor prognosis.

Highlights

Reversible phosphorylation was well known to regulate protein function and transfer cell signal
A total of 212 articles were retrieved by a literature search of the PubMed, Embase, and Web of Science databases, using the search strategy as follow: (KIAA1524 protein OR “Cancerous inhibitor of protein phosphatase 2A” OR cancerous inhibitor of protein phosphatase 2A (CIP2A)) AND AND
The 22 studies provided a sample of 4579 patients to assess the relationship between CIP2A expression and solid tumor prognosis

Summary

Introduction

Reversible phosphorylation was well known to regulate protein function and transfer cell signal. Serine/threonine protein phosphatase 2A (PP2A) was a cancer inhibitor which play a critical role in inhibition of cell malignant transformation via negatively regulating several major signaling pathways involved in the cancer progression [2]. CIP2A interacted directly with the oncogenic transcription factor MYC, inhibited PP2A activity toward MYC serine 62 (S62), and thereby prevented MYC proteolytic degradation [6]. This function contributed to consequent effects on different signaling pathway such as PI3K-AKT-mTOR pathway and RAS-MEK-ERK pathway [7]. Some have shown no association with patient prognostic significance [37, 38] and even improved prognosis in nodular melanomas [29] The results of those individual studies were controversial. We performed this comprehensive meta-analysis to evaluate the prognostic value of CIP2A in solid tumors

Materials and methods

Results

I-IV I-IV I-III

Discussion