Genome wide expression analysis of human pancreatic cancer with bioinformatics tools

Pancreatic cancer is a highly metastatic malignancy with a very poor prognosis and low survival rate, which is difficult to diagnose and treat. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is a cancer with a very poor prognosis. The one-year survival rate is approximately 18%. Since the disease does not show symptoms in the early period, it is usually in the 3rd or 4th stage when diagnosed. In such pathologies, where early diagnosis is very important, the patient is lost soon (6-12 months) after the diagnosis of the disease. The most important reason for this situation is that non-invasive molecular biomarkers (genes) that can be used in the early diagnosis of pancreatic cancer have not been detected, so the disease can usually be detected in the advanced or metastatic stage. In this sense, only 20% of patients diagnosed with pancreatic cancer are suitable for surgical resection. Local and distant metastases are seen in most of the patients at the time of diagnosis. There is no non-invasive screening test that can be used to diagnose pancreatic cancer. In pancreatic cancer, CA 19-9, P53, K-ras and microRNAs are the most frequently studied and associated tumor markers with pancreatic cancer. CA 19-9 is the most preferred serum marker for diagnosis. However, the specificity and sensitivity of this marker to pancreatic cancer is questionable. Serum carbohydrate antigen CA 19–9 (CA 19–9) is a tumor-associated antigen, also known as Lewis a-antigen. CA 19-9 is normally secreted from cells of the pancreas, bile duct, stomach, colon, endometrium, salivary glands, and bronchial epithelium. CA 19–9 is the most commonly used tumor marker in the diagnosis of pancreatic cancer. CA 19–9 is not only specific for pancreatic adenocarcinomas, but may also be elevated in many tumors caused by the gastrointestinal tract. It is also associated with blood group antigens of CA 19-9. CA 19-9 synthesis does not occur in individuals with the genotype Lewis a-b-. Therefore, this patient group can be evaluated with false results. Again, CA 19-9 is not very sensitive in small pancreatic tumors. In recent years, studies on new tumor markers have been carried out. The effect of genetic changes in cell proliferation and growth on the development of cancer is known. The function of oncogenes, increase in their stimulation, inhibition of tumor suppressor genes, changes in DNA repair mechanisms and defects in genes responsible for apoptosis are responsible for the basic molecular pathology of cancer. Another marker, K-ras, as a guanine nucleotide binding protein, takes part in growth factor signal transduction. With this function, cell proliferation increases and resistance to apoptosis develops. K-ras is the most frequently detected mutated oncogene in human cancers. Mutations in the K-ras oncogene are detected in approximately 90% of cancers of pancreatic ductal origin, and it becomes important especially in the early stages of carcinogenesis. K-ras mutation can be detected not only in pancreatic tissue cells, but also in pancreatic fluid, duodenal brush biopsies, blood and stool samples. As the cellular type increases, the K-ras oncogene mutation rate also increases. Today, in the diagnosis of pancreatic cancer; Ultrasound, EUS, CT, ERCP, MR and fine needle aspiration are used. However, these methods do not give a clue for early diagnosis of the disease. In our study, in silico analyzes were performed using the raw transcriptome data in the NCBI GEO DataSet database. In these analyzes, the expression profiles of pancreatic cancer and normal tissue and blood samples were compared, and genes with different expression levels were determined between these two groups. Gene Set Enrichment Analysis, Hierarchical Cluster Analysis and Pathway Analysis were performed using these gene lists which obtained from different datasets. The validation of the genes in the determined candidate gene list as a result of these bioinformatics analyzes was validated by QRT-PCR using both blood and tumor tissue samples of pancreatic cancer patients. In this way, information about the molecular mechanisms that play a role in both the formation of pancreatic cancer and the prognosis process can be obtained, and important data can be obtained about the molecular subtypes of pancreatic cancer. Recently, intensive studies have been carried out to determine the molecular subtypes of pancreatic cancer. In some of these studies, it was stated that this cancer has 3 different molecular subtypes, and in some, it has four different molecular subtypes. However, since the studies on this subject are relatively new, there is not enough data on this subject. Therefore, for the future, it is of great importance to develop a non-invasive, accurate and specific molecular biomarker that is specific for pancreatic cancer and has a high potential for clinical application.