Abstract
The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a five year survival rate of less than 5%. Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. Though many serum markers have been reported to be elevated in patients with PC, so far, most of these markers have not been implemented into clinical routine due to low sensitivity or specificity. In this study, we have identified genes that are significantly upregulated in PC, through a meta-analysis of large number of microarray datasets. We demonstrate that the biological functions ascribed to these genes are clearly associated with PC and metastasis, and that that these genes exhibit a strong link to pathways involved with inflammation and the immune response. This investigation has yielded new targets for cancer genes, and potential biomarkers for pancreatic cancer. The candidate list of cancer genes includes protein kinase genes, new members of gene families currently associated with PC, as well as genes not previously linked to PC. In this study, we are also able to move towards developing a signature for hypomethylated genes, which could be useful for early detection of PC. We also show that the significantly upregulated 800+ genes in our analysis can serve as an enriched pool for tissue and serum protein biomarkers in pancreatic cancer.
Highlights
The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor and resistance to cytotoxic drugs all contribute to the high mortality rate of Pancreatic cancer (PC)
The identification of driver mutations and the cancer genes that they alter has been a central aim of cancer research; so far, about 500 (2%) of the 22,000 protein-coding genes in the human genome are reported to show recurrent mutations in cancer with strong evidence that these contribute to cancer development [9]
Two outliers were identified by this method, namely, Buchholz Pancreas (Pancreatic Ductal Adenocarcinoma) and Buchholz Pancreas (Pancreatic Intraepithelial Neoplasia)
Summary
Pancreatic cancer (PC) is a highly lethal malignancy, and patients with PC have a 5-year survival rate of less than 5% [1]. The mutations found in a cancer cell genome have generally accumulated over the lifetime of the cancer patient and usually number between 1,000–10,000 [4]. The identification of driver mutations and the cancer genes that they alter has been a central aim of cancer research; so far, about 500 (2%) of the 22,000 protein-coding genes in the human genome are reported to show recurrent mutations in cancer with strong evidence that these contribute to cancer development [9] (http://www.sanger.ac.uk/ genetics/CGP/Census/). Studies in mice have suggested that more than 2,000 genes, when appropriately altered, may have the potential to contribute to cancer development [10] indicating that the search for cancer genes is far from over. The proteins altered by driver mutations have become targets for successful anticancer drug development [11,12,13]
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