GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer

Colorectal cancer(CRC)is the third most frequently diagnosed cancer worldwide,responsible for over 880000 deaths each year.Growth/differentiation factor 15(GDF-15)is reported to be a promising diagnostic and prognostic factor in CRC.It induces pleiotropic effects in tumor cells:proliferation,sternness,invasion and metastasis.Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms.However,it has not been investigated in CRC yet.The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-la(HIF-1α),VEGF-A and chemokine-like receptor 1(CMKLR1)in tumor and margin specimens of CRC in relation to histological grade and TNM staging.The study comprised 33 samples of tumor and margin tissues obtained from CRC patients.To assess the concentration of GDF-15,HIF-1α,VEGF-A and CMKLR1,commercially available enzyme-linked immunosorbent assay(ELISA)kits were used.We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue.The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue.In CRC,the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α,VEGF A and CMKLR1 expression.Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC.The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors.

Specific metabolic biomarkers as risk and prognostic factors in colorectal cancer

Advances in genomics,molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value.Epidemiological and biological studies suggest a role for adiposity,dyslipidaemia,hyperinsulinemia,altered glucose homeostasis,and elevated expression of insulin-like growth factor(IGF)axis members in the risk and prognosis of cancer.This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders.The authors describe three main systems as the most studied metabolic candidates of carcinogenesis:dyslipidemias,adipokines and insulin/IGF axis.However,each of these components is unsuccessful in defining the diseases risk and progression,while their co-occurrence increases cancer incidence and mortality in both men and women.

Potential role of human papilloma virus in the pathogenesis of gastric cancer

AIM: To demonstrate the presence and biological activity of human papilloma virus (HPV) in gastric cancer (GAC) tissues.

The Transcriptional Activity of LAMP3 Gene Involved in Autophagocytosis in Colorectal Cancer LAMP3 Expression in Colorectal Cancer

Background: Autophagocytosis is a biological process involving the controlled distribution of cell fragments and organelles in order to obtain an additional source of energy. LAMP3 (lysosome-associated membrane protein 3) is a heavily glycosylated integral membrane protein located mainly in the lysosomal membrane. Recent studies have shown that it participates in tumor metastasis and drug resistance. Its main role is contribution to tumor cells proliferation, migration and invasion. The aim of this study was to determine changes in transcriptional activity of LAMP3 at various stages of colorectal cancer. In addition, an attempt was made to select miRNAs potentially regulating LAMP3 expression using bioinformatic databases. Methods: The study was conducted on healthy colon samples and colon cancer samples in four stages. Molecular analysis included the extraction of total RNA, purification of the obtained extracts, expression profile analysis using oligonucleotide microarray technique and in silico determination of miRNAs potentially regulating the LAMP3 expression. Results: The level of LAMP3 expression is higher in colorectal adenocarcinoma cells than in non-cancerous cells and depends on the stage of the disease. Conclusions: LAMP3 may promote cancer progression, metastasis and cause the resistance to treatment.