Low tumour PPM1H indicates poor prognosis in colorectal cancer via activation of cancer-associated fibroblasts

Background Vimentin (VIM) is considered a prognostic marker in colorectal cancer (CRC). Our aim is to identify genes that fulfil a “X-low implies VIM-high” Boolean relationship and to evaluate their prognostic value and potential mechanism. Methods Potential biomarkers related to VIM expression were searched using a bioinformatics approach across gene-expression arrays. Based on subgroup analysis of 2 CRC cohorts, the selected gene was tested for its association with patient’s survival outcomes. The regulatory link between the selected gene and VIM was further examined with in vitro models. Results PPM1H was identified as the top candidate in our search. Patients with PPM1H-low tumours have a lower 5-year disease-free survival rate than patients with PPM1H-high tumours in 2 independent cohorts. In multivariate Cox analysis, patients with PPM1H-low tumours were independently associated with relapse in both the discovery cohort (hazard ratio [HR], 1.362; 95% confidence interval [CI], 1.015–1.826; P = 0.039) and the validation cohort (HR for DFS, 4.052; 95% CI, 2.634–6.234; P