Upregulation and the clinical significance of KCNQ1OT1 and HAGLROS lncRNAs in papillary thyroid cancer: An observational study.

Long noncoding RNAs (lncRNAs) play an important role in regulating gene expression. Changes in their expression have been associated with many types of cancer, including thyroid cancer. This study aimed to investigate how changes in the expression of potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) and HAGLR opposite strand lncRNA (HAGLROS) lncRNAs correlate with the development and clinicopathological characteristics of papillary thyroid cancer (PTC). Reverse transcription-quantitative polymerase chain reaction was used to investigate the expression of lncRNAs in both tumor and adjacent normal thyroid tissue samples of the patients. Expressions of KCNQ1OT1 and HAGLROS were upregulated in the patients tumor samples compared to the adjacent normal thyroid samples. KCNQ1OT1 expression was linked to microcarcinoma and gender, while HAGLROS expression was linked to microcarcinoma and tumor size. When only microcarcinoma samples were evaluated, KCNQ1OT1 expression was higher in tumor tissues compared to normal tissues; however, no significant difference was observed in HAGLROS expression. Our data suggests that high expressions of KCNQ1OT1 and HAGLROS might contribute to the development of PTC and disease progression, and both lncRNAs may be potential therapeutic targets in PTC patients.

Expression of SOX2OT, DANCR and TINCR long non­coding RNAs in papillary thyroid cancer and its effects on clinicopathological features.

Long non­coding RNAs (lncRNAs) are molecules that are >200 base pairs long and do not encode a protein. However, they perform important roles in regulating gene expression. Recent studies have revealed that the changes in the expressions of lncRNAs serve a role in the development and metastases of a number of types of cancer. A number of studies have been published on the association of SOX2 overlapping transcript (SOX2OT), differentiation antagonizing non­protein coding RNA (DANCR) and tissue differentiation­induced non­coding RNA (TINCR) expression with various types of cancer. However, researchers have not yet studied their roles in papillary thyroid cancer or at least, those roles are not clarified. The aim of the present study was to investigate the expression and clinical significance of SOX2OT, DANCR and TINCR in papillary thyroid cancer (PTC). A total of 102 patients with PTC were included in the present study. Reverse transcription­quantitative PCR method was used to determine the relative gene expression levels of lncRNAs and then the relationship between expressions of lncRNAs and clinical characteristics of the subjects was analyzed in detail. Expression levels of SOX2OT (P=0.016) and DANCR (P=0.017) increased in the tumor samples in contrast to the normal tissues. No significant difference was observed in the expression level of TINCR (P=0.298). In addition, SOX2OT expression was associated with micro carcinoma (P<0.001), tumor size (P=0.010) and primary tumor (P=0.006), while DANCR expression was associated with age (P=0.030) and micro carcinoma (P=0.004). The findings of the present study indicated that DANCR may contribute to the development of PTC while SOX2OT may contribute to both the development and progression of PTC.

Possibility of paclitaxel to induce the stemness-related characteristics of prostate cancer cells.

BACKGROUND: Drug resistance poses a crucial problem in the treatment of prostate cancer. Recent studies have shown that chemotherapy agents may cause cancer cells to acquire stem cell-like properties, resulting in drug resistance and, eventually, treatment failure. OBJECTIVES: To evaluate whether long-term paclitaxel exposure causes an increase in the stem cell-like properties of prostate cancer cells. MATERIAL AND METHODS: Paclitaxel-resistant PC-3 cells were generated from parental PC-3 cells by treating them with increasing concentrations of paclitaxel. The expression levels of the stem cell markers NANOG, C-MYC, CD44, and ABCG2 were evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). A sphere formation assay was performed to test the potential of the cells to behave as stem cells, and a wound healing assay was carried out to evaluate migration ability of the cells. RESULTS: The expression levels of C-MYC and NANOG were significantly higher in paclitaxel-resistant PC-3 cells compared to the parental PC-3 cells. However, there was no significant increase in the expression of CD44 or ABCG2. In addition, the sphere-forming capacity and migration ability of resistant PC-3 cells were increased. CONCLUSIONS: The results of the current study indicate that paclitaxel exposure may increase the stem cell-like properties of PC-3 prostate cancer cells.

Postmenopausal estrogen receptor positive breast cancer and obesity associated gene variants.

Obesity is one of the most important health risks in postmenopausal women. Molecular pathways that are connected with obesity are believed to interact with the pathogenesis of breast cancer (BC). The aim of this research was to study the polymorphisms of two obesity-associated genes ADIPOQ and FTO that are also related to the pathogenesis of BC. Obesity-associated gene polymorphisms ADIPOQ rs1501299 and rs2241766, and FTO rs1477196, rs7206790, rs8047395, and rs9939609 were studied in 101 Turkish postmenopausal estrogen receptor-positive BC patients and 100 healthy control individuals. ADIPOQ rs1501299 was detected to be associated with protection against BC. The ADIPOQ rs1501299 TT genotype, the rs2241766 GT genotype and the G allele were found to be significantly higher in the control group. In addition, ADIPOQ rs1501299 polymorphism was protective in the recessive model and rs2241766 polymorphism was protective in the dominant model. While none of the FTO gene polymorphisms were found to be associated with BC, the frequencies of rs9939609 A allele and rs7206790 G allele were correlated with body mass index (BMI) in BC patients. ADIPOQ rs1501299 TT genotype, rs2241766 GT genotype, and G allele might be protective against BC in the Turkish population but this conclusion needs to be further verified.

Low-penetrance susceptibility variants and postmenopausal oestrogen receptor positive breast cancer.

The risk of breast cancer (BC) in women is high and many factors including genetic factors increase the risk for the disease. It is revealed that the variations of low-penetrance susceptibility genes are important for carcinogenesis as they interact with the environmental and hereditary factors. Recently, the list of BC-associated common single nucleotide polymorphisms (SNPs) and chromosomal loci in low-penetrance susceptibility genes have been expanded in genomewide association studies. FGFR2, LSP1, MAP3K1, TGFB1, TOX3, 2q35 and 8q loci variations are some examples for these common SNPs. These SNPs and their association with BC risk was investigated in many different populations. Therefore in this study, we aimed to evaluate low-penetrance susceptibility SNPs; namely FGFR2 rs1219648, rs2981579, rs2981582; MAP3K1 rs889312; TOX3 rs3803662; LSP1 rs909116, rs3817198 and SLC4A7 rs4973768 together, for the firsttime in Turkish postmenopausal oestrogen receptor positive BC cases. Following the DNA isolation, multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) based SNP analysis were performed. MAP3K1 rs889312 SNP demonstrated the strongest association with BC risk among the other low penetrant SNPs, it was also associated with BC risk in a dominant model. Only in a ressesive model, TOX3 rs3803662 was associated with BC risk. In addition, rs4973768 CC and rs909116 CC genotypes are correlated with higher tumour size which is not reported in the literature as yet; on the other hand there are no associations between any of the other SNP genotypes and clinopathological parameters. In our opinion, MAP3K1 rs889312 may be a good BC susceptibility biomarker candidate for Turkish population.

Genetic Variations of DNA Repair Genes in Breast Cancer.

Genetic variations in DNA repair genes may affect DNA repair capacity therefore increase risk for cancer. In our study, we evaluted the relation between DNA repair gene polymorphisms XRCC1 rs1799782, rs25487, rs25489; XPC rs2228000, rs2228001; XPD rs1799793, rs13181; XRCC3 rs861539; RAD51B rs10483813, rs1314913 and breast cancer risk for 202 Turkish cases in total, in which 102 patients with breast cancer and 100 controls. Genotyping of the DNA samples was carried out by multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) using Sequenom MassARRAY 4 analyzer. Genotype and allele distributions were calculated between the groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. rs25487 AA genotype and A allele was found to be increased in the control group (respectively, OR 0.16 95% CI 0.02-1.06, p = 0.058; OR 1.55, 95% CI 1.01-2.36, p = 0.043) and rs861539 T allele was found to be decreased in the patient group (OR 1.53, 95% CI 1.01-2.30, p = 0.049). No association with breast cancer was found for the remaining SNPs. Our findings suggest that XRCC1 rs25487 AA genotype and A allele, XRCC3 rs861539 T allele may have protective effects in breast cancer for Turkish population.

Association of B7-H4 gene polymorphisms in urothelial bladder cancer.

BACKGROUND/AIM: We aimed to study polymorphisms of the B7-H4 gene in order to evaluate a possible association in urothelial carcinoma, as it is highly expressed in cancer tissues. MATERIALS AND METHODS: In this study B7-H4 gene rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a control group including 30 patients without bladder cancer. RESULTS: We detected that the rs10754339 polymorphism was more frequent in the cancer patients when compared with the control group (P < 0.05). Only the rs3738414 polymorphism showed a statistically significant difference in frequency between pathologic diagnostic groups. CONCLUSION: The rs10754339 AA genotype distribution was found to have a higher frequency whereas the rs3738414 AG genotype distribution was lower in the bladder cancer group (P < 0.05). None of the genotype distributions showed a significant difference from the control group for the rs10801935 polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic marker in urothelial carcinoma.

An investigation of the effects of FGFR2 and B7-H4 polymorphisms in breast cancer.

INTRODUCTION: Polymorphisms in FGFR2 are important markers for breast cancer susceptibility in the general population. CHEK2 and FGFR2 polymorphisms with known susceptibility alleles of BRCA1, BRCA2, PTEN, and TP53, can be investigated as potential modifiers of high penetrant risk alleles. Although the B7-H4 gene is highly expressed in many different tumors, there is one published study showing the association of polymorphisms with breast cancer. We aimed to investigate FGFR2 and B7-H4 polymorphisms in breast cancer in the Turkish community. MATERIALS AND METHODS: In a group of 31 cases diagnosed with breast cancer and 30 healthy women with matched ages, the single-nucleotide polymorphisms (SNPs) rs1219648, rs2981582 in FGFR2 gene were identified by sequence analysis and the SNPs rs10754339, rs10801935, and rs3738414 in the B7-H4 gene were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was performed using SPSS. RESULTS: Although statistically not significant, the frequency of FGFR2 heterozygous polymorphisms in the group with breast cancer was detected to be higher. In the B7-H4 SNP rs10801935, polymorphic AA, and AG genotype distributions were found in higher frequencies in the breast cancer patients. In contrast to the results of a published study, the present study shows that B7-H4 rs3738414 polymorphism GG genotype was found in higher frequency in the control group than the breast cancer group and the result was statistically significant (P=0.018). CONCLUSION: Larger scale studies are necessary to determine the prevalence of these polymorphisms and association with breast cancer in Turkish community, as this study is the first study performed.

Surgery for acute abdomen and MEFV mutations in patients with FMF.

OBJECTIVES: Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent fever, peritonitis, arthritis, pleuritis, and secondary amyloidosis. In the current study, we sought to determine the frequency of acute surgical abdominal intervention and MEFV gene mutations in FMF patients. PATIENTS AND METHODS: A total of 159 patients were referred to our department with a diagnosis of FMF. Twenty-six patients (16.4%) had a history of surgical intervention. Of these, 17 (10.7%) were operated on due to appendicitis, and 9 (5.7%) were operated on due to other acute abdomen reasons. Genomic DNA was isolated from the blood samples, and in the isolated DNA samples, 12 MEFV gene mutations were studied. RESULTS: Mutation frequency was detected to be 80.8% in the patients with acute abdomen surgery intervention and 56.4% in the patients without acute abdomen surgical intervention. Upon mutational evaluation of these patients, we noted that the M694V (40.5%) and E148Q (21.4%) mutations occurred most frequently. CONCLUSIONS: The MEFV gene mutation frequency in FMF patients with acute abdomen surgical intervention was significantly higher than that in patients without such intervention. Increased mutation scanning in FMF patients will significantly decrease unnecessary surgical interventions in this patient group.