Plasma Levels of Kynurenine, Soluble OX40 and Mir-138-5p Are Associated With Tumor-infiltrating Lymphocytes in Colorectal Cancer: An Exploratory Study.

BACKGROUND/AIM: Colorectal cancer (CRC) is one of leading cancers in terms of incidence and mortality. Interaction of tumor cells with the surrounding microenvironment plays a crucial role in the development and progression of CRC. Many pathways such as the kynurenine pathway, OX40/OX40L-mediated signaling and microRNAs targeting PD-L1 may be involved in CRC development by affecting T cell activation, thus creating an immune-deficient microenvironment. Herein, our goal was to assess the association between plasma levels of tryptophan (TRP), kynurenine (KYN), KYN/TRP ratio, soluble OX40 (sOX40) and PD-L1-targeting miR-138-5p and CRC risk. PATIENTS AND METHODS: Plasma concentrations of TRP and KYN were determined by HPLC; sOX40 was measured by ELISA whereas circulating miR-138-5p was measured by quantitative PCR in pathologically confirmed CRC patients and colonoscopy-verified CRC-free controls without polyps (control group 1) and with polyps (control group 2). RESULTS: We found significantly lower plasma levels of TRP in CRC patients compared to control groups which resulted in significantly higher KYN/TRP ratio in CRC patients than in the controls (p=0.007). Plasma levels of sOX40 did not significantly differ between groups. The levels of circulating miR-138-5p were significantly lower in CRC patients (relative median value 0.02) than in the control groups (relative median values 0.2 and 4.29, respectively) (p=0.03). Plasma levels of KYN and sOX40 were considerably higher in patients with no tumor-infiltrating lymphocytes (TILs) than those with TILs whereas circulating miR-138-5p had opposite expression pattern in plasma. CONCLUSION: The kynurenine pathway and miR-138-5p are associated with CRC risk and plasma levels of KYN, sOX40 and miR-138-5p are related to TILs, making them possible target molecules in possible immunotherapeutic targets for CRC.

lncRNA NORAD, soluble ICAM1 and their correlations may be related to the regulation of the tumor immune microenvironment in laryngeal squamous cell carcinoma (LSCC).

NORAD, non-coding RNA activated by DNA damage, is a Long non-coding RNA (lncRNA) transcript that modulates genome stability and has been reported to be dysregulated in different cancers. Although it has been reported to be upregulated in tumor cells mostly for solid organ cancers, it has also been reported to be downregulated in some cancers. Although the pathophysiological mechanism is not fully understood, a negative correlation between NORAD and intercellular cell adhesion molecule-1 (ICAM-1) has been shown in experimental models, but this situation has not been evaluated in terms of cancer. We aimed to evaluate the potential roles of these two biomarker candidates together and separately in the clinicopathological axis in Laryngeal squamous cell carcinoma (LSCC) in a case-control study setting. The interactions of NORAD and ICAM1 at the RNA level were evaluated interactively by the RIblast program. sICAM1 (soluble intercellular cell adhesion molecule-1) levels were determined by ELISA in one hundred and five individuals (forty-four LSCC, sixty-one control) and lncRNA NORAD expression in eighty-eight tissues (forty-four LSCC tumors, forty-four tumor-free surrounding tissues) was determined by Real-time PCR. While the energy treesholud was - 16 kcal/mol between NORAD and ICAM1, the total energy was 176.33 kcal/mol, and 9 base pair pairings from 4 critical points were detected. NORAD expression level was found to be higher in tumor surrounding tissue compared to tumor tissue, and sICAM1 was higher in the control group compared to LSCC (p = 0.004; p = 0.02). NORAD discreminte tumor surrounding tissue from tumor (AUC: 0.674; optimal sensitivity:87.50%; optimal specificity 54.55%; cut-off point as >1.58 fold change; P = 0.034). The sICAM1 level was found to be higher in the control (494,814 ± 93.64 ng/L) than LSCC (432.95 ± 93.64 ng/L) (p = 0.02). sICAM1 discreminte control group from LSCC (AUC: 0.624; optimal sensitivity 68,85%; optimal specificity 61,36%; cut-off point ≤115,0 ng/L; (p = 0.033). A very strong negative correlation was found between NORAD expression and patients' sICAM1 levels (r = -.967; n = 44; p = 0.033). sICAM1 levels were found to be 1.63 times higher in NORAD downregulated subjects compared to upregulated ones (p = 0.031). NORAD was 3.63 times higher in those with alcohol use, and sICAM 1 was 5.77 times higher in those without distant organ metastasis (p = 0.043; 0.004). The increased NORAD expression in the tumor microenvironment in LSCC, the activation of T cells via TCR signaling, and the decrease of sICAM in the control group in correlation with NORAD suggests that ICAM1 may be needed as a membrane protein in the tumor microenvironment. NORAD and ICAM1 may be functionally related to tumor microenvironment and immune control in LSCC.

Predicting the predisposition to colorectal cancer based on SNP profiles of immune phenotypes using supervised learning models.

This study explores the machine learning-based assessment of predisposition to colorectal cancer based on single nucleotide polymorphisms (SNP). Such a computational approach may be used as a risk indicator and an auxiliary diagnosis method that complements the traditional methods such as biopsy and CT scan. Moreover, it may be used to develop a low-cost screening test for the early detection of colorectal cancers to improve public health. We employ several supervised classification algorithms. Besides, we apply data imputation to fill in the missing genotype values. The employed dataset includes SNPs observed in particular colorectal cancer-associated genomic loci that are located within DNA regions of 11 selected genes obtained from 115 individuals. We make the following observations: (i) random forest-based classifier using one-hot encoding and K-nearest neighbor (KNN)-based imputation performs the best among the studied classifiers with an F1 score of 89% and area under the curve (AUC) score of 0.96. (ii) One-hot encoding together with K-nearest neighbor-based data imputation increases the F1 scores by around 26% in comparison to the baseline approach which does not employ them. (iii) The proposed model outperforms a commonly employed state-of-the-art approach, ColonFlag, under all evaluated settings by up to 24% in terms of the AUC score. Based on the high accuracy of the constructed predictive models, the studied 11 genes may be considered a gene panel candidate for colon cancer risk screening.

Significance of Intercellular adhesion molecule-1 Lys496Glu gene polimorphism on plasma redox status regulation in laryngeal carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The present research is conducted to investigate whether specific gene polymorphism of ICAM-1 K469E (rs5498) and plasma redox status could be associated with laryngeal cancer (LC) development. Since there is no clear evidence which investigates the relationship between ICAM-1 polymorphism and ROS-mediated plasma protein oxidation in LC, our study is the first significant contribution for investigating the relationship. METHODS: The study covered patients with primary LC and their age-matched healthy control subjects. Evaluation of ICAM-1 K469E (rs5498) gene polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Plasma redox status was assessed with spectrophotometric methods. RESULTS: In the current paper, we found that LC patients with GG genotype had a decreasing trend for the plasma oxidative damage biomarker levels when compared with all allele genotypes (AA and AG). CONCLUSION: We concluded that G allele of the ICAM-1 K469E gene plays a significant role in the optimal regulation of plasma redox homeostasis in patients with LC.

Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer.

Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n = 159) and controls (n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 µmol/L, kynurenine level was 1.33 ± 0.02 µmol/L, and the kynurenic acid level was 0.01 ± 0.001 µmol/L. The level of tryptophan was found to be low in CRC compared to control (p < .001). In cases with CRC, CC genotype (p = .048) and C allele (p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) (p = .021).We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.

Investigation of Long Non-coding RNAs H19 and LINC00675 in Colorectal Cancers in Terms of Histopathological Features and Correlations With Plasma Markers.

BACKGROUND/AIM: Functional and bioinformatic studies provide strong evidence that long non-coding RNAs (lncRNAs) can alter the molecular mechanisms of cancer through their interactions with DNA, RNAs, and proteins. This study aimed to evaluate the role of H19 and LINC00675 lncRNAs in colorectal cancers (CRCs) in terms of clinicopathological features. MATERIALS AND METHODS: Tumor and tumor-free surrounding tissue samples were obtained from 51 CRC cases. Total RNA isolation and cDNA synthesis were performed. qPCR was performed using the TaqMan non-coding lncRNA assay specific for H19 and LINC00675. Preoperative levels of plasma markers, lncRNA expression, and clinicopathological characteristics of the cases were evaluated statistically. RESULTS: Expression of H19 in tumor tissue was found to be 2.11 times higher than that of tumor-free surrounding tissue (p<0.001). LINC00675 levels were found to be approximately three times higher in colon tumors than tumors with rectal involvement (p=0.019). There was a correlation between H19 expression and creatinine (r=0.408; p=0.003). In addition, correlations were detected between LINC00675 with albumin (r=0.303; p=0.03), and between LINC00675 with globulin (r=0.332; p=0.02). CONCLUSION: H19 is a candidate biomarker that can be evaluated in terms of prognosis and antineoplastic treatment response, while LINC00675 may be an important marker of the microenvironment of advanced stage tumors, especially in tumors with rectal involvement.

Potential role of immune cell genetic variants associated with tumor microenvironment response in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features.

Immunomodulatory signals regulate the self-tolerance, activation, priming and survival processes of T cells. Programmed cell death protein 1 (PD1), Programmed death-ligand 1 (PD-L1) inhibitory signals and CD27, CD28 costimulators have been detected for many solid organ cancers in tumor-infiltrating T cells. It was aimed to investigate the immune cell-based regulatory genetic variants in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features. Genotyping was performed by PCR-RFLP method for PD-1 rs2227981, PD-L1 rs2890658, CD28 rs3116496, CD27 rs2267966 genetic variants from genomic DNAs extracted from peripheral blood samples in One Hundred Thirty-Six individuals (Sixty-one LSCC and seventy-five controls). Analysis of SNPs was carried out according to multiple inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). There was no difference between LSCC and control groups in genotype/allele distribution for PD-1 and PD-L1 (p > 0.05). In the PD-1 overdominant model, the CT genotype was found to be high (p = 0.036) in those without a family history. The frequency of C allele (AC+CC) in the PD-L1 dominant model was higher in alcohol users and those with reflux (p = 0.024; p = 0.001 respectively). In the Dominant model for PD-L1, the AA genotype was lower in moderately and well-differentiated tumors than in poorly differentiated tumors (p = 0.02). CD27 AT and CD28 CT genotypes were found to be higher in LSCC patients compared to the control group (p = 0.009; p = 0.01 respectively), while linkage disequilibrium (LD) was detected between CD27 and CD28 (p = 0.02). In the CD28 dominant model, C allele (CT+CC) carriage was found to be high in those with family history and in those without reflux and perineural invasion (p = 0.01; p = 0.01; p = 0.03 respectively). In LSCC, PD-L1 rather than PD-1 has a prognostic effect in terms of clinicopathology, and the LD and clinicopathological relationships detected between CD28 and CD27 genotypes suggest that the hereditary immune checkpoint-dependent T cell traffic may be pathophysiologically important.

The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer.

BACKGROUND: The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. METHODS: The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. RESULTS: The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p<0.0001). The patients with rs4644 CA/CC (p<0.0001 and p<0.0001) and rs4652 AA/AC (p=0.001 and p<0.0001) genotypes had higher serum galectin-3 levels than their corresponding controls. Serum galectin-3 levels increased in the presence of vascular invasion in patients with both rs4644 AC (p=0.03) and rs4652 AC (p=0.019) genotypes. The receiver operating characteristic curve suggested serum galectin-3 level as a strong predictive marker for the patient group with a cut-off value of 17.089 ng/mL (area under the curve: 0.910±0.04; 95% confidence interval: 0.832-0.988; p<0.001). Univariate analysis revealed the association of lower serum galectin-3 levels with better survival (p=0.048). Multivariate survival analysis showed that only high serum galectin-3 levels tended to be related to survival of the patients (hazard ratio: 5.106; 95% confidence interval: 0.956-27.267; p=0.056). CONCLUSION: The presence of galectin-3 gene variants may lead to histopathological differences among patients with non-small cell lung cancer. Serum galectin-3 level may be a valuable diagnostic biomarker and be associated with survival of these patients.

Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression.

Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with ß-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.

Effect of trail C1595T variant and gene expression on the pathogenesis of non-small cell lung cancer.

It is known that disorders in apoptosis function play an important role in the pathogenesis of many types of cancer, including lung cancer. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), a type II transmembrane protein, is a death ligand capable of inducing apoptosis by activating distinctive death receptor. Our purpose in this study is to investigate the gene polymorphisms in TRAIL molecular pathway and TRAIL gene expression levels in non-small cell lung cancer (NSCLC) patients in terms of pathogenesis and prognosis of the disease. In this study, TRAIL C1595T polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis in 158 patients with NSCLC and 98 healthy individuals. Surgically resected tissues were examined and classified histopathologically. In addition, TRAIL gene expression levels in tumor tissue and tumor surrounding tissue samples of 48 patients with NSCLC were determined using real-time polymerase chain reaction. TRAIL gene expression levels of NSCLC patients were detected significantly 28.8 fold decrease in the tumor tissue group compared to the control group (p=0.026). When patients were compared to tumor stage, expression of TRAIL gene in advanced tumor stage was found to be significantly 7.86 fold higher than early tumor stage [p=0.028]. No significant relationship was found between NSCLC predisposition and prognostic parameters of NSCLC with TRAIL genotypes, but the frequency of TRAIL gene 1595 CT genotype was observed to be lower in the patients compared to the other genotypes, and the difference was found to be very close to statistical significance (p=0.07). It can be suggested that TRAIL may play an important role in the development of NSCLC and may be an effective prognostic factor in tumor progression.: It is known that disorders in apoptosis function play an important role in the pathogenesis of many types of cancer, including lung cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein, is a death ligand capable of inducing apoptosis by activating distinctive death receptor. Our purpose in this study is to investigate the gene polymorphisms in TRAIL molecular pathway and TRAIL gene expression levels in non-small cell lung cancer (NSCLC) patients in terms of pathogenesis and prognosis of the disease.

A Study of Short- and Long-term mRNA Levels of the Retn, Iapp, and Drd5 Genes in Obese Mice Induced with High-fat Diet.

BACKGROUND/AIM: Adipocyte gene expression is altered in obese individuals through multiple metabolic and biochemical pathways. In this study, we aimed to examine the expression of resistin (Retn), amylin (Iapp), and dopamine receptor domain 5 (Drd5) genes previously suggested to contribute to the pathogenesis of obesity, albeit controversially. We also aimed to determine the effects on short and long-term mRNA levels of these genes in obese mice, induced with high-fat diet (HFD). MATERIALS AND METHODS: Two obesity models were created in our study: group T1 (20 mice) was fed with HFD (60% fat) for 3 months, and group T2 (20 mice) was fed with HFD (60% fat) for 6 months. The control group T0 (20 mice) was fed with a diet of 10% kcal fat supplement for 6 months. At the end of the experiment, their adipose tissues were dissected surgically. Tissue samples of each group were pooled for RNA isolation, cDNA synthesis was carried out and the mRNA levels were examined by quantitative real-time polymerase chain reaction. Serum resistin levels were measured using multiplex bead (luminex) technology for validation. RESULTS: In T2 mice, the mRNA expression of Retn showed a moderate up-regulation (fold change=8.32; p=0.0019) in the adipose tissues. Iapp expression was also significantly up-regulated (fold change=9.78; p=0.012). Moreover, a 6.36-fold up-regulation for Drd5 was observed in the adipose tissues of T2 mice (p<0.001). At the same time, serum levels of resistin were found to be high in T1 and T2 mice compared to the control group (p<0.001 and p=0.024, respectively). CONCLUSION: Our study demonstrated that the mRNA levels of the genetic markers considered to play a role in adipogenesis were different in short- and long-term obesity models formed in C57BL/6J mice using HFD.

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients.

BACKGROUND: This study aims to investigate the possible relationships between epidermal growth factor receptor gene mutations, serum epidermal growth factor receptor levels, programmed death ligand gene expression levels and the risks and survivals of resectable nonsmall cell lung cancer patients. METHODS: Deoxyribonucleic acid isolation was performed from peripheral blood samples and tumor tissues. The mutation analysis was performed for epidermal growth factor receptor. Programmed death ligand 1 gene expression levels were examined pathologically and histopathologically following the tissue tracing of 36 non-small cell lung cancer patients (29 males, 7 females; mean age 60.1 years; range, 41 to 79 years) and analyzed using real-time polymerase chain reaction. Epidermal growth factor receptor serum levels were assessed in all patients. RESULTS: As a result of mutation analyses in 21 patients (28.5% of all adenocarcinoma patients), epidermal growth factor receptor mutation was determined in at least one exon in six patients. In epidermal growth factor receptor mutation detected patients, programmed death ligand 1 gene expression levels were associated with lymph node metastasis (p=0.036). However, epidermal growth factor receptor mutations were not statistically significantly associated according to histopathological examination (p>0.05). Of patients carrying exon 20 (c.2303G>T) mutations, 25% had tumors with perineural invasion. There was a statistically significant association between exon 20 insertions and c.2303G>T and lymphatic invasion (p=0.02), lymph node metastasis and exon 20 insertions (p=0.03). Patients with lower serum epidermal growth factor receptor levels (<400 pg/mL) had better survival time than those with higher serum epidermal growth factor receptor levels (p=0.04). CONCLUSION: Programmed death ligand 1 gene expression and epidermal growth factor receptor mutation might have a combined effect on non-small cell lung cancer. Programmed death ligand 1 gene expression in tumor pathology may also be a significant feature for tumor progression and tumorigenesis. Serum epidermal growth factor receptor levels seem to be associated with survival.

MMP-3 gene polymorphisms and Osteosarcoma.

Osteosarcoma (OSA) is the most common adolescence cancer among all primary bone tumors next only to multiplemyeloma. It has a substantially worse prognosis and ability to metastasize to lung. MMPs (matrix metalloproteinases) are among the major proteases that take part in regulation of ECM (extracellular matrix). MMPs play an active role in the formation of the osteoid tissue, rich in collagens and other ECM proteoglycans. They also take part in pro-osteoclast, osteoclast, osteoblast, and osteoid formation. Many members of the MMP gene family have been linked to human cancers. It has been shown that MMPs particularly play a role in the tumor's acquisition of an invasive and metastatic character. In our study, the E45K and T102T polymorphisms of MMP-3 were studied using the PCR-RFLP method in 135 Turkish subjects (54 subjects with osteosarcoma and 81 healthy controls). We found that frequencies of E45K G allele (p:0,010, χ²:6,710, OR:1,429, 95% Cl: 1,019-1,858) and AG genotype (p:0,001, χ²:14,753, OR:2,32, 95% Cl: 1,491-3,626) were elevated in patients compared to controls. Besides, there was a significant difference in.E45K AA genotype between study groups (p:0,004, χ²:8,182, OR: 2,929, 95% Cl: 1,38-6,19). There were no significant differences between any genotypes or allele in the control and patient groups for MMP-3 T102T polymorphism. Our findings indicate that the G allele and AG genotype of MMP-3 E45K polymorphism is associated with increased risk of osteosarcoma in adolescent population of Turkey.

LGALS3 and AXIN1 gene variants playing role in the Wnt/ ß-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer.

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ ß-catenin pathway by binding to ß-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the ß-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ ß-catenin pathway in the pathogenesis of colorectal cancer.

Association of SUMO4 M55V and -94ins/del gene variants with type-2 diabetes.

AIM: There are two different types of diabetes mellitus, type 1 and type 2, with still unclear molecular mechanisms. In the present study, we aimed to investigate the role of small ubiquitin-like modifier 4 (SUMO4) M55V and nuclear factor kappa B1 (NFKB1)-94del/ins in type-2 diabetes mellitus. MATERIALS AND METHODS: We analyzed SUMO4 M55V and NFKB1-94del/ins variants in 104 patients with type-2 diabetes and 124 healthy controls using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. RESULTS: The number of SUMO4 M55V MM genotype and M allele carriers was significantly higher in patients compared to the control group; however, no efficiency results were found related to NFKB1-94del/ins polymorphism. CONCLUSION: It was found that SUMO4 M55V polymorphism and type-2 diabetes were significantly associated with a possible SUMO4 region to type-2 diabetes susceptibility. This preliminary study showed that the distribution of SUMO4 M55V and type-2 diabetes mellitus in Turkish patients may form the basis of future research.