Project description:This is a human single cell sequencing repository of pancreatic cancer tumor tissue and PBMCs of pancreatic cancer patients. The goal of this study was to thorough map the immune landscape of pancreatic ductal adenocarinoma patient tumors and peripheral blood.
Project description:RNA seq gene expression analysis of patients with resected pancreatic cancer following 1 dose of GM-CSF expressing whole cell pancreatic vaccine 2 weeks prior to resection. Samples were obtained for IHC analysis of protein expression, IHC analysis of immune cell infitration and RNA sequencing correlates
Project description:Pancreatic cancer is the fourth leading cancer-related death in United States. The clinical relevance of genomic imbalances in pancreatic cancer is uncertain. We performed array-comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens from a Korean cohort. We observed recurrent copy number gains were observed in chromosome 1q, 11q, 18q11.1-11.2, and 20q13.13; and losses in chromosome 2p, 9p, 10q, 14q, 15q, 18q12.2-23, 19q, 20q11.1, 21p, and 22q. High copy number gains, with log2 ratio >2.0, were observed in 4 cytobands, encoding genes such as G protein-coupled receptor 48, c-myc and gamma-catenin. By comparing the aCGH results of long survivors and short survivors, determined according to the median survival, we observed that loss of cytoband 18q22.3, encoding 5 genes, was the only alteration with significantly different frequencies. The copy number of the CPGL (Carboxypeptidase of glutamate-like) gene in cytoband 18q22.3 was found to be significantly associated with overall survival in univariate analyses (p=0.019 by log-rank test). This was subsequently assessed in the Italian cohort: 41 out of the 61 specimens carried deletion of the CPGL gene. Patients with deletion of the CPGL gene also had shorter overall survival (p=0.003 by log-rank test). Multivariate analysis of the two cohorts combined showed that loss of 18q22.3 / deletion of the CPGL gene was an independent poor prognostic factor for overall survival after adjusting for other factors which were found to impact the outcome (hazard ratio 2.72, p=0.0007). overexpression of the CPGL or its alternating splicing isoform CPGL-B in a pancreatic cancer cell lines resulted in slower proliferation of cells, G1 cell cycle arrest, and reduced migration activity. In conclusion, through aCGH analysis, we identified loss of 18q22.3 / deletion of the CPGL gene as potentially being an independent poor prognostic factor in resected pancreatic cancer. We further identified the CPGL gene as a potential tumor suppressor for pancreatic cancer cell lines. Array-comparative genomic hybridization was performed in 44 resected pancreatic cancer specimen from a Korean cohort. Genomic alteration relating to prognosis of the Korean cohort was further validated in a Italian cohort containing 61 resected pancreatic cancer specimens.
Project description:Despite extensive biological and clinical studies, including comprehensive genomics and transcriptomics analysis, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with poor survival and no effective therapies to date. Correlation networks are emerging as a powerful approach to infer tumor biology and to prioritize candidate genes as biomarkers or drug targets. In this study we applied a weighted co-expression analysis to the functionally relevant proteome of 20 surgically resected patients with PDAC. We obtained twelve modules with overlapping yet distinct biology, which implicated metabolism and ECM complexes in several modules. Notably, one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p=0.01) and was validated in public RNA data (p=0.02). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 radically resected patients.
Project description:Despite extensive biological and clinical studies, including comprehensive genomics and transcriptomics analysis, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with poor survival and no effective therapies to date. Correlation networks are emerging as a powerful approach to infer tumor biology and to prioritize candidate genes as biomarkers or drug targets. In this study we applied a weighted co-expression analysis to the functionally relevant proteome of 20 surgically resected patients with PDAC. We obtained twelve modules with overlapping yet distinct biology, which implicated metabolism and ECM complexes in several modules. Notably, one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p=0.01) and was validated in public RNA data (p=0.02). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 radically resected patients.