MTP6.15 Werner Syndrome Protein, WRN, in clinical colorectal cancer and its value in patient’s clinical outcome and response to therapies

Introduction The WRN (Werner syndrome) protein, coded by the WRN gene, is a reason for the autosomal recessive early ageing condition and linked with certain cancer types. WRN may cooperate with p53 in regulating apoptosis in cancer cells. Here, we investigated WRN expression colon cancer and explored the therapeutic implications. Methods and results Expression of the WRN gene transcripts was quantitatively determined in a cohort of colorectal cancer and analysed against a range of clinical and pathological factors including tumour stage, differentiation as well as the clinical outcome of the patients. The relationship between WRN expression and patients’ therapeutic response was also assessed from the TCGA database. Statistical analyses were by non-parametric methods. Colon cancer tissues had significant a marked aberration in WRN expression when compared with normal colon tissues (p<0.0001 by Mann-Whitney test). There was a progressive reduction of WRN in Dukes B and Dukes C tumours compared with Dukes A tumours and progressive reduction from poorly differentiated to highly differentiated tumours (p<0.001 by ANOVA test). Patients with low levels of WRN were seen with shorter survivals but were mainly in the subgroup with low levels of ERBB2 and high levels of ERBB4. Finally, high levels of WRN in colon cancer and cancer cells is a good indicator for a sensitive response to topoisomerase inhibitor such as Irinotecan. Conclusion WRN expression in colon cancer is aberrant. High level of WRN is a favourable indicator for the clinical outcome and sensitivity to selective drugs.