PO-501 Loss of SOX9 expression is a predictive marker of relapse in gastric cancer

Introduction Gastric cancer is one of the most frequent tumours and the third leading cause of cancer-related death worldwide. The investigation of new biomarkers that can predict patient outcome more accurately and allow better treatment and follow-up decisions is of crucial importance. The transcription protein SRY-box 9 (SOX9) is a member of the high-mobility-group box class DNA-binding proteins. SOX9 is an important regulator of cell-fate decisions in embryogenesis and adulthood, playing critical roles in differentiation and proliferation, also in the gastrointestinal tract. SOX9 has been correlated to tumour behaviour in different tissues, including in gastric cancer, nevertheless with contradictory results. In this work we sought to ascertain the relevance of SOX9 transcription factor as a prognostic marker in gastric cancer. Material and methods SOX9 expression was analysed by immunohistochemistry in a series of 333 cases of gastric adenocarcinoma, and its association with clinico-pathological and follow-up data was evaluated. A second gastric cancer validation cohort consisted of 354 cases from the cancer genome atlas (TCGA), showing high versus low SOX9 expression. Results and discussions SOX9 expression was present in 83% of gastric cancer cases. Loss of SOX9 expression was significantly associated with relapse, however SOX9 expression was more frequent in stage IV cases. SOX9 loss of expression predicted worse disease-free survival but not overall survival, in this series. The prognostic value of SOX9 was independent of Lauren classification but it was more pronounced in tumours with expansive versus infiltrative growth (p=0.008). In patients that presented with disease in stage I to III, loss of SOX9 expression was significantly associated with venous invasion and lymph node metastases. In an independent series of gastric cancer, where SOX9 expression was assessed at the mRNA level (TCGA), low SOX9 expression levels were also associated with poor patient outcome. Functional studies, after down- and up-regulation of SOX9, are now being undertaken in order to better understand the clinico-pathological observations and the relevance of SOX9 as a potential biomarker in gastric cancer. Conclusion We have identified SOX9 as a marker of relapse in gastric cancer. Further experiments are needed to elucidate its biological relevance at the cellular level and to test its potential role in invasion.