Dataset Information

Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.

ABSTRACT: Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case-control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-free DNA samples. Quantitative real-time reverse transcription-polymerase chain reaction was performed to determine the expression of KRAS transcripts in eutopic endometrial tissue. Our results suggest that the variant is not associated with the development of endometriosis in Iranian women. We observed higher levels of KRAS messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis compared to controls. Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity.

SUBMITTER: Farahani MS

PROVIDER: S-EPMC4502798 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.

Farahani Maryam Shahrabi MS Shahbazi Shirin S Moghaddam Soheila Amini SA Mahdian Reza R

Reproductive sciences (Thousand Oaks, Calif.) 20141030 6

Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case-control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-fr ...[more]

PMID: 25361550

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Project description:BackgroundLethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC.Patients and methodsWe analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.ResultsA total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995).ConclusionThis analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.

Project description:Cancer is a genetic disease that is highly influenced by environmental factors. To determine the risk factors of squamous cell carcinoma of the head and neck, two polymorphisms, solute carrier family 23 member 2 (SLC23A2-05 [rs4987219]) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-LCS6 (rs61764370), and environmental factors, including smoking and alcohol consumption, were studied in a population. The present study included 165 males diagnosed with squamous cell carcinoma of the head and neck. The control group consisted of 230 healthy male subjects without cancer or a family history of cancer. The SLC23A2-05 and KRAS-LCS6 polymorphisms were analyzed by polymerase chain reaction followed by enzymatic digestion. All patients and healthy subjects were assessed with regard to their smoking habit and alcohol consumption as these are considered to be risk factors for cancer. The statistical analysis was performed using logistic regression, Fisher's exact and ?2 tests. Additional analyses were performed using the programs, multi-factor dimensionality reduction (MDR; version 2.0) and MDR permutation test (version 0.4.7), which consider all variables as risk factors simultaneously. The results of the present study demonstrate that the SLC23A2-05 and KRAS-LCS6 polymorphisms are not a risk factor for squamous cell carcinoma of the head and neck. In the same samples, the association of alcohol consumption (P<0.001) and smoking habit (P<0.001) with cancer presence was positive when each variable was considered individually. Concerning the environmental factors, a positive association of smoking habit and alcohol consumption with cancer, although not with ethnicity (ratio, 1.0244; testing balance accuracy, 0.8733; P<0.001) was identified using the MDR tool, which analyzed the variables and polymorphism genotypes simultaneously. In conclusion, in the present study, squamous cell carcinoma of the head and neck was highly affected by environmental factors when compared with the affect of SLC23A2-05 and KRAS-LCS6 polymorphisms.

Project description:BackgroundVaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis.ObjectivesWe aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes.DesignA total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group).MethodsData regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey.ResultsA similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination.ConclusionWomen with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.

Dataset Information

Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.

Publications

Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.

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