Researching the roles of stem cell related factors in the formation of colon cancer

Colon cancer (CC), is the third most common cause of cancer death in the world. Colon cancer mostly originates from colon polyps. Even though its etiology is one of the most known among cancers; causing about one million new cases and over five hundred thousand deaths per year reveals the need to clarify this issue better. Therefore, new studies are needed for diagnosis, treatment and prognosis in this process. Most of colon cancers caused by adenomatous or neoplastic of polyps (NP). NP histologically divided as tubular, villous and tubulovillous. Turning into invasive carcinoma for polyp is associated with its histologic type and size. All adenomas have abnormal gland structure with varying degrees and dysplasia, which is manifested with intracellular structural damage. The degree of dysplasia determines the transformation of adenoma to cancer; high-grade dysplasia (HGD) has higher risk of turning into cancer when compared with low-grade dysplasia (LGD). Adenoma–carcinoma sequence can not be explained only by mutations in certain genes, so epigenetic changes must be considered. One of the most important factors in the formation of cancer are tumor-initiating cells or cancer stem cells (CSC). CSC, which have self-renewing ability, are responsible from the onset of tumors, differentiation, invasion, metastasis, relapse and resistance to treatment in many cancers. Despite being in a very small amount of cancer tissue, they are seen as one of the most important cause of cancer treatment failure. In our study transcription factor genes (OCT4, KLF4, SOX2, MYC, NANOG and REX1) and cell surface markers (CD133, LGR5), which are associated with embryonic stem cells, induced pluripotent stem cells and cancer stem cells, have been selected for measuring expression levels from the selected tissues. The aim of this project is to identify the differences in expression levels of stem cell related factors (SCRF) in normal colon tissue, histopathologically staged colon polyps and colon cancer, and to explain the roles of SCRFs in the formation of CC for elucidating the formation of CC and for contributing the effectively usage of SCRFs in the diagnosis and treatment of CC. After isolation of total RNA from FFPE tissues, SCRF expressions was measured by RT-qPCR method. SCRF expression differences was determined in normal colon-polyp-cancer transformation. SCRF expression studies in colon cancer are inadequate, inconsistent and often include CC and normal tissues. In this study it is our aim to determine the important factors in the formation of cancer with measuring SCRF expressions in histopathologically graded(HGD-LGD) normal colon-polyp-cancer tissues. We think determining the SCRF expression differences in the formation of colon cancer, may contribute to the diagnosis, treatment and prognosis of CC. This study shows that the increase of cancer SCRF expression occurs together with HGD and villous features. Villous and especially HGD-displaying polyps support why cancer susceptibility is high. Increased expression levels of LGR5, PROM1, and MYC in HGD and cancerous tissues support poor prognosis and demonstrate that they can be used to assess diagnosis and prognosis. LGR5 and PROM1 expresses the presence of tumor-initiating cells and coexpression of stem cell-associated factors indicate the presence of cancer stem cells and poor prognosis. Identification of tissue-specific SCRF expressions will help design gene therapies to control the development and progression of colonic neoplasia.