Fig. 1: PPP2R2B downregulation confers risk of disease progression and poor treatment response to anti-HER2 therapy.

a Volcano plot illustrating hazard ratio (log₂) compared with P value (−log₁₀) between expression of PP2A members and relapse-free survival (RFS) in breast cancer. Members whose downregulation is significantly (Bonferroni-adjusted P value < 0.05) prognostic are highlighted in red, and their gene names are indicated next to their representative dots. Data were collected from KM Plotter (http://kmplot.com/analysis/). The computed based performing thresholds which are used as cut-offs were auto-selected for the percentiles of the subjects between the low and high gene-expression groups. b P value (−log₁₀) between expression of the indicated subunit genes and distant metastasis-free survival (DMFS) in different breast cancer molecular subtypes. The molecular subtypes presented include basal-like (Basal), luminal A (LumA), luminal B (LumB), and HER2+ (HER2). P < 0.01 is considered statistically significant. c Kaplan–Meier curves comparing DMFS of breast cancer patients with tumors expressing the indicated levels of PPP2R2B in the indicated breast cancer subtypes. Data from b and c were collected from the GOBO database (http://co.bmc.lu.se/gobo/gsa.pl). P values in a to c were calculated with two-sided log-rank test. d RT-qPCR measuring expression of PPP2R2B in treatment-naïve primary HER2 + breast cancer tumors (n = 16) vs. distant metastatic tumors that recurred after a trastuzumab-containing regimen (n = 7). Data are expressed as means ± s.d. P value was calculated with two-sided Mann–Whitney U test. e Correlation analysis (n = 29) of PPP2R2B expression assessed by RT-qPCR and reduction of tumor size after two cycles of lapatinib-containing regimen in a HER2+ breast cancer cohort from a phase II clinical trial (ClinicalTrials.gov; Identifier: NCT01309607). The qPCR was performed with pre-amplified cDNA products. Correlation coefficient r and P value were calculated with Pearson correlation test. f Two-sided Chi-Square test of the relationship between low expression of PPP2R2B and residual disease (RD) after a neoadjuvant trastuzumab-containing regimen, in a HER2+ breast cancer cohort. pCR: pathologic complete response. High or Low PPP2R2B expression is defined with a cut-off of a Z-score of −0.5. Data are from microarray dataset GSE62327 available on Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/).