Is CIP2A a biomarker for poor prognosis in cancer? – A systematic review with meta-analysis

Background Cancerous inhibitor of PP2A (CIP2A) is a trimeric protein phosphatase inhibitor. CIP2A acts on the tumor suppressor PP2A, controlling cell survival and proliferation. Several studies have demonstrated that CIP2A is aberrantly overexpressed in both hematological cancers and solid tumors and may be a predictive biomarker for poor prognosis. On the other hand, there are several studies that show conflicting evidence. This comprehensive systematic review aims to evaluate the predictive significance of CIP2A in cancer. Methods 34 studies published from 2013 to 2026, were selected for the examination of the potential relationship between CIP2A and various clinical milestones in solid and hematological cancers. Searches of PubMed, EBSCO (Medline) and Web of Science (core collection) were conducted until 01/06/2026. The Newcastle-Ottawa scale was used to assess risk of bias. Meta-analysis was performed to evaluate the use of CIP2A as a predictive biomarker for clinical outcome. Results At 5 years, the random effects model revealed a significant difference between low and high CIP2A expression and overall survival (OS) (p < 0.001). At one and 5 years, there were significant differences in progression free survival (PFS) between low and high CIP2A expression (P = 0.001 and P < 0.001, respectively). Subgroup analysis revealed that, in the context of both the colorectal and breast cancer groups, there were significant differences between the low and high CIP2A groups at the five-year milestone and in CML and AML at 1 year. Conclusion Elevated CIP2A expression at diagnosis was associated with poor overall survival and progression-free survival, although this association should be interpreted cautiously due to heterogeneity between cancer types, limited subgroup data, and methodological limitations. When compared to several other cancers, it was discovered that this association was stronger in specific cancers, such as leukemia, colorectal and breast cancer.