Abstract

Tumour purity is defined as the proportion of cancer cells in the tumour tissue. The impact of tumour purity on colon cancer (CC) prognosis, genetic profile and microenvironment has not been thoroughly accessed. Therefore, clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA were retrospectively collected (n = 1248). Tumour purity of each sample was inferred by a computational method based on transcriptomic data. Stage III and MMR-deficient (dMMR) CC patients showed a significantly lower tumour purity. Low purity CC conferred worse survival and tumour purity was identified as an independent prognostic factor. Moreover, high tumour purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumour purity with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumour purity. Furthermore, immune-related pathways and immunotherapy-associated markers (PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumour purity. Therefore, tumour purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity related microenvironmental changing.\n\nSummaryLow purity colon cancer patients conferred worse survival and benefited less from adjuvant chemotherapy. The mutation burden was negatively associated with tumour purity. Low purity samples exhibited intense immune phenotype with more M2 macrophages and neutrophils infiltration.