Aims: Cancer stem-like cells (CSC) are a sub-population of self-renewing, quiescent cancer cells with tumourigenic potential. Quiescence describes a process of slow-cycling cell division in CSC which increases their chemoresistance. Recent studies have demonstrated that the pluripotency-associated transcription factor SOX2 identifies quiescent CSC populations in cancer. In a previous study involving 316 stage II/III colon cancer patients, we found that SOX2+ cell density in tumours may identify patients with poorer prognosis and those less likely to benefit from chemotherapy (unpublished data). In this study we aim to validate these findings in a larger, independent cohort of patients.
Methods: The validation cohort consists of 816 patients with stage II/III colorectal cancer (CRC) and at least 13 years follow-up. Tissue micro-arrays (TMAs) were immunohistochemically stained for SOX2 expression and quantified using StrataQuest digital image analysis software. Overall and cancer-specific survival were assessed using Kaplan-Meier estimates and Cox proportional hazards regression.
Results: Our previous study demonstrated that high SOX2 expression was associated with poor survival (HR 1.645; 95%CI 1.01-2.69, p = 0.046) and that 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). Findings from the current validation study will be presented.
Conclusions: SOX2 is a strong CSC marker candidate due to its role in inducing pluripotency in adult cells and to identify quiescent, chemoresistant cancer cells. Our preliminary data indicate that SOX2 may be a useful marker in CRC to identify patients with poor prognosis and those less likely to benefit from chemotherapy. Validation of these results would support further investigation of the role SOX2 plays in CRC to determine potential clinical or therapeutic applications.