Cancer stem-like cells (CSC) are a sub-population of self-renewing cancer cells that have enhanced tumourigenic capacity. In colon cancer, interactions with tumour-infiltrating lymphocytes can influence the ability of CSC to survive treatment and form secondary tumours. Here we investigated the prognostic value of CSC markers and immune-related markers in stage II/III colon cancer.
Expression of the putative CSC markers CD133, SOX2, ALDH1, CD44v6 and Lgr5, the T cell markers CD3, CD8 and Foxp3, and programmed death ligand-1 (PD-L1) was assessed in tissue samples from 316 patients with stage II/III colon cancer by immunohistochemistry. Tissue micro-arrays were used and marker expression was digitally quantified using image analysis software. Associations with overall and cancer-specific survival were assessed using Kaplan-Meier estimates and Cox proportional hazards regression.
High SOX2 expression was associated with poor survival (HR 1.645; 95%CI 1.01-2.69, p=0.046) whereas high Foxp3 and high PD-L1 expression were associated with improved survival (HR 0.48, 95%CI 0.24-0.98, p=0.043 and HR 0.45, 95%CI 0.22-0.91, p=0.025, respectively). Patients whose tumours expressed high SOX2 and low PD-L1 had a particularly poor prognosis compared to all other groups (HR 4.01, 95%CI 1.81-8.90, p=0.0006). When cases were stratified based on SOX2 expression, patients with SOX2Low tumours demonstrated a significant benefit from adjuvant chemotherapy (HR 0.56, 95%CI 0.32-0.97, p=0.040) whereas those with SOX2High tumours did not (p=0.973).
These results suggest that SOX2 may be a useful prognostic marker for patients with colon cancer, particularly when the state of the local tumour immune response is taken into account. In this cohort, SOX2 was strongly associated with benefit from adjuvant chemotherapy, supporting further investigation of this CSC marker as a predictor of chemotherapy response.