The Prognostic and Predictive Value of SOX2 + Cell Densities in Patients Treated for Colorectal Cancer

• Published in: Cancers Vol. 12; no. 5; p. 1110
• Main Authors: Miller, Tim J, McCoy, Melanie J, Lee-Pullen, Tracey F, Anyaegbu, Chidozie C, Hemmings, Christine, Bulsara, Max K, Platell, Cameron F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-04-2020; MDPI
• Subjects: 5-Fluorouracil; Cancer therapies; Cell density; Chemotherapy; Colon cancer; Colorectal cancer; Colorectal carcinoma; Homeobox; Image processing; Medical prognosis; Oxaliplatin; Patients; Pluripotency; Prognosis; Stem cells; Studies; Survival analysis; Transcription factors; Tumors; 5-fluorouracil; SOX2; colorectal cancer; cancer stem cell; oxaliplatin; chemotherapy; prognosis
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12051110

SOX2 (sex-determining region-Y homeobox-2) is a transcription factor essential for the maintenance of pluripotency and is also associated with stem-cell-like properties in preclinical cancer models. Our previous study on a cohort of stage III colon cancer patients demonstrated high SOX2
cell densities were associated with poor prognosis. However, most patients were treated with adjuvant chemotherapy so the prognostic value of SOX2 could not be assessed independently from its value as a predictive marker for non-response to chemotherapy. This study aimed to assess whether SOX2 was a true prognostic marker or a marker for chemotherapy response in a historical cohort of patients, a high proportion of whom were chemotherapy-naïve. SOX2 immunostaining was performed on tissue micro-arrays containing tumor cores from 797 patients with stage II and III colorectal cancer. SOX2
cell densities were then quantified with StrataQuest digital image analysis software. Overall survival was assessed using Kaplan-Meier estimates and Cox regression. It was found that high SOX2
cell densities were not associated with poor overall survival. Furthermore, all patients had a significant improvement in survival after 5-fluorouracil (5-FU) treatment, irrespective of their SOX2
cell density. Therefore, SOX2
cell densities were not associated with prognosis or chemotherapy benefit in this study. This is in contrast to our previous study, in which most patients received oxaliplatin as part of their treatment, in addition to 5-FU. This suggests SOX2 may predict response to oxaliplatin treatment, but not 5-FU.