Supplementary Table S1. Primers sequences used in the real-time PCR. Supplementary Table S2. siRNA oligoes used in the study. Supplementary Table S3. Primers sequences used in the quantitative ChIP. Supplementary Table S4. Clinicopathological features and correlation of MUC16 expression in PDAC in the TCGA cohorts. Supplementary Table S5. Univariate and multivariate Cox regression of Overall survival for patients with PDAC in the TCGA cohorts. Supplementary Table S6. Clinicopathological features and correlation of MUC16 expression in PDAC in the FUSCC cohorts. Supplementary Table S7. Univariate and multivariate Cox regression of Overall survival for patients with PDAC in the FUSCC cohorts.
ARTICLE ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a devastating disease with the 5-year survival rate less than 6%. Previous results indicated that serum levels of CA125 (encoded by MUC16) could be used to predict which groups of pancreatic cancer patients may benefit from surgery. However, the underlying mechanism remains elusive. Herein, using the Cancer Genome Atlas and clinicopathologic data obtained from our center, we demonstrate that high CA125 serum levels and expression levels of MUC16 are predictive of poor prognosis. MUC16 is also validated as a downstream target of KRAS, and their expression strongly correlated with each other in vitro and in vivo. Mechanistically, the KRAS/ERK axis induced upregulation of MUC16 and shedding of CA125 via its effector c-Myc in SW1990 and PANC-1 pancreatic cancer cells. Notably, proto-oncogene c-Myc could bind to the promoter of MUC16 and transcriptionally activate its expression. Taken together, these data establish CA125 as a prognostic marker for pancreatic cancer, and mechanistic studies uncovered the KRAS/c-Myc axis as a driving factor for upregulation of MUC16.Implications: The current study uncovers the contribution of oncogenic KRAS to serum marker CA125 production through a mechanism that involves the ERK/c-Myc axis. Mol Cancer Res; 15(2); 201–12. ©2016 AACR.