Yixing Wu1, Huatian Huang2, Beatrice Fervers, Lingeng Lu3. 1. From the Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou. 2. Department of Diagnostic Imaging, Guizhou Qianxinan People's Hospital, Xingyi, China. 3. Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Center for Biomedical Data Science, Yale Cancer Center, Yale University, New Haven, CT.
Abstract
OBJECTIVES: The purpose of this study was to investigate the association of syndecan-1 (SDC1) and KRAS molecular characteristics with patient survival in pancreatic cancer. METHODS: Both SDC1 mRNA and methylation and KRAS mRNA and somatic mutations, as well as clinical data were retrieved from The Cancer Genome Alta pancreatic cancer data set for survival analyses. Kyoto Encyclopedia of Gene and Genomes pathway analysis for coexpressed genes for either SDC1 or KRAS was performed, respectively. RESULTS: A significantly negative correlation existed between SDC1 mRNA and DNA methylation. Patients with KRAS somatic mutations had a significantly higher SDC1 mRNA but lower methylation than those without the mutations. Compared with patients with KRASSDC1 signature, those with a high level of KRAS and SDC1 alone or both had a significantly elevated mortality. The adjusted hazard ratios (95% confidence interval) were 2.30 (1.16-4.54, P = 0.017) for KRASSDC1, 2.85 (1.48-5.49, P = 0.002) for KRASSDC1, and 2.48 (1.31-4.70, P = 0.005) for KRASSDC1, respectively. Several Kyoto Encyclopedia of Gene and Genomes pathways were shared, whereas there were distinct pathways between KRAS and SDC1 coexpressed genes. CONCLUSIONS: SDC1 interplays with KRAS, and targeting both KRAS and SDC1 in combination may be more beneficial to pancreatic cancer patients.
OBJECTIVES: The purpose of this study was to investigate the association of syndecan-1 (SDC1) and KRAS molecular characteristics with patient survival in pancreatic cancer. METHODS: Both SDC1 mRNA and methylation and KRAS mRNA and somatic mutations, as well as clinical data were retrieved from The Cancer Genome Alta pancreatic cancer data set for survival analyses. Kyoto Encyclopedia of Gene and Genomes pathway analysis for coexpressed genes for either SDC1 or KRAS was performed, respectively. RESULTS: A significantly negative correlation existed between SDC1 mRNA and DNA methylation. Patients with KRAS somatic mutations had a significantly higher SDC1 mRNA but lower methylation than those without the mutations. Compared with patients with KRASSDC1 signature, those with a high level of KRAS and SDC1 alone or both had a significantly elevated mortality. The adjusted hazard ratios (95% confidence interval) were 2.30 (1.16-4.54, P = 0.017) for KRASSDC1, 2.85 (1.48-5.49, P = 0.002) for KRASSDC1, and 2.48 (1.31-4.70, P = 0.005) for KRASSDC1, respectively. Several Kyoto Encyclopedia of Gene and Genomes pathways were shared, whereas there were distinct pathways between KRAS and SDC1 coexpressed genes. CONCLUSIONS:SDC1 interplays with KRAS, and targeting both KRAS and SDC1 in combination may be more beneficial to pancreatic cancerpatients.