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Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.
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Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.
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Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.
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Objective The aim of this study was to explore the expression,prognosis and related function of Linc00152 in breast cancer.Methods Thirty-three cases of breast specimens were selected for RNA-Sequencing.The expression of Linc00152 was detected by qPCR in 50 pairs of breast cancer tissues and adjacent tissues.Combined with GEO and TCGA databases,the correla-tion between Linc00152 expression and the degree of malignancy and the prognosis of patients was analyzed.Cell proliferation,apopto-sis and cell migration were detected in breast cancer MDA-MB-231 cell line,gastric cancer SGC-7901 cell line and renal cell carcinoma 786-O cell line.Results Linc00152 was highly expressed in breast cancer(P<0.001),and was higher in HER2 posi-tive and triple negative breast cancer(P<0.001).In patients with high expression of Linc00152,the event-free survival and the me-tastasis-free survival were very poor(P<0.001,P<0.01).After knockdown Linc00152,the cell proliferation,migration and inva-sion were decreased and the apoptosis was increased(P<0.05).Conclusion Linc00152 has a role of promoting cancer in malignant tumors and may be a potential therapeutic target.
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In the context of precision medicine, although individual treatment of breast cancer under the guidance of molecular classi-fication has become the norm, a precision treatment program with increased efficiency and quality is still required. Compared with the traditional real-time fluorescent quantitative polymerase chain reaction (PCR), the droplet digital PCR (ddPCR) has obvious advantages in the detection of rare mutations and copy number variations, as well as the integration with the second-generation-sequencing tech-nology. This paper reviews the application of a ddPCR platform in different breast cancer subtypes and explores new horizons of breast cancer research through the ddPCR technology.
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PURPOSE: Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. METHODS: Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. RESULTS: Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. CONCLUSION: The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls.
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Humans , Area Under Curve , Biomarkers , Breast Neoplasms , Breast , MicroRNAs , Real-Time Polymerase Chain Reaction , Receptors, Progesterone , ROC Curve , Sensitivity and SpecificityABSTRACT
Objective The aim of this study was to investigate the association between single nucleotide polymorphisms(SNPs)in FGFR3 gene and the risk of breast cancer.Methods The frequency of SNP genotypes rs2234909 and rs3135848 of FGFR3 gene in premenopausal breast cancer patients and premenopausal normal fe-males were detected by multiple clonal extension SNP typing technique.The SNP genotypes were compared with different SNP genotypes and the risk of premenopausal breast cancer.Results There was no difference in the genotype frequencies of SNP rs 2234909 and rs3135848 between breast cancer and control groups(P>0.05).Lo-gistic regression analysis showed that there was no correlation between TC and TC +CC genotype and risk of breast cancer(OR=1.035,95% CI:0.680~1.575,P=0.874;OR=0.985,95% CI:0.638~1.521,P=0. 945).For the rs3135848 locus,the genotypes of TC,CC and TC+CC were not associated with the risk of breast cancer(OR=1.177,95%CI:0.846-1.636,P=0.333;OR=0.948,95% CI:0.287-3.137,P=0.931;OR=1.162,95%CI:0.548~1.112,P=0.360).Histological grade was significantly higher in breast cancer with rs2234909 mutation than that of the non-mutation group(dominant model:P=0.032,co-dominant model:P=0.024).The Ki67 index of FGFR3 gene locus rs2234909 mutation was higher than that of the non-mutation (dominant model:P=0.056;co-dominant model:P=0.044).There was no difference between rs3135848 mu-tation and both site mutation with clinicopathological features of breast cancer patients(P>0.05).Conclusion The SNP genotypes of rs2234909 and rs3135848 of FGFR3 gene were not associated with susceptibility to breast cancer in premenopausal women in North of China.Rs2234909 mutation was positively correlated with histological grade and Ki67 index in premenopausal breast cancer patients.
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Objective The aim of this study was to investigate the association between single nucleotide polymorphisms(SNPs)in FGFR3 gene and the risk of breast cancer.Methods The frequency of SNP genotypes rs2234909 and rs3135848 of FGFR3 gene in premenopausal breast cancer patients and premenopausal normal fe-males were detected by multiple clonal extension SNP typing technique.The SNP genotypes were compared with different SNP genotypes and the risk of premenopausal breast cancer.Results There was no difference in the genotype frequencies of SNP rs 2234909 and rs3135848 between breast cancer and control groups(P>0.05).Lo-gistic regression analysis showed that there was no correlation between TC and TC +CC genotype and risk of breast cancer(OR=1.035,95% CI:0.680~1.575,P=0.874;OR=0.985,95% CI:0.638~1.521,P=0. 945).For the rs3135848 locus,the genotypes of TC,CC and TC+CC were not associated with the risk of breast cancer(OR=1.177,95%CI:0.846-1.636,P=0.333;OR=0.948,95% CI:0.287-3.137,P=0.931;OR=1.162,95%CI:0.548~1.112,P=0.360).Histological grade was significantly higher in breast cancer with rs2234909 mutation than that of the non-mutation group(dominant model:P=0.032,co-dominant model:P=0.024).The Ki67 index of FGFR3 gene locus rs2234909 mutation was higher than that of the non-mutation (dominant model:P=0.056;co-dominant model:P=0.044).There was no difference between rs3135848 mu-tation and both site mutation with clinicopathological features of breast cancer patients(P>0.05).Conclusion The SNP genotypes of rs2234909 and rs3135848 of FGFR3 gene were not associated with susceptibility to breast cancer in premenopausal women in North of China.Rs2234909 mutation was positively correlated with histological grade and Ki67 index in premenopausal breast cancer patients.
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Objective The relationship between the clinicopathological features and the prognosis of breast cancer patients was evaluated by the expression of EPB41L4A-AS2 in breast cancer tissues.Methods The relationship between the expression of EPB41L4A-AS2 and the clinical features of breast cancer was evaluated by using the genome meta analysis,TCGA and Gene Expression Library(GEO) datasets.The correlation between EPB41L4A-AS2 and apoptotic pathway was verified by Western blotting.Results The results from Meta -analysis,TCGA and GEO datasets showed that EPB41L4A-AS2 was low in breast cancer tissues and was positively correlated with poor clinical and pathological features.EPB41L4A-AS2 was confirmed an association with the classical apoptosis pathway in breast cancer cell lines.In the meta-analysis of GEO,we found the high expression of EPB41L4A-AS2 with good prognosis.Conclusion EPB41L4A-AS2 inhibits tumor formation and has a high value in clinical prognosis of breast cancer.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is inconsistently associated with increased risk of adverse pregnancy outcomes. The purpose of this meta-analysis was to summarize the evidence regarding the strength of the association between pregnancy in women with PCOS and pregnancy complications. METHODS: We systematically searched PubMed, EmBase, and the Cochrane Library to identify observational studies up to January 2016. The primary focus was pregnancy outcomes, including gestational diabetes mellitus (GDM), preeclampsia, pregnancy-induced hypertension (PIH), preterm delivery, cesarean delivery, oligohydramnios, and polyhydramnios. Effect estimates were pooled using the random-effects model. The analysis was further stratified by factors that could affect these associations. RESULTS: We included 40 observational studies that reported data on a total of 17,816 pregnancies with PCOS and 123,756 pregnancies without PCOS. Overall, PCOS in pregnancy was associated with greater risk of GDM, preeclampsia, PIH, preterm delivery, cesarean delivery, miscarriage, hypoglycemia, and perinatal death. However, PCOS in pregnancy had little or no effect on oligohydramnios, polyhydramnios, large-for-gestational age (LGA), small-for-gestational-age (SGA), fetal growth restriction (FGR), preterm premature membrane rupture, fasting blood glucose (FBG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, total cholesterol, congenital malformation, macrosomia, and respiratory distress syndrome. Subgroup analysis suggested that these associations might be influenced by study design and pre-BMI. CONCLUSION: PCOS in pregnancy is associated with a significantly increased risk of adverse pregnancy, fetal, and neonatal outcomes.
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Polycystic Ovary Syndrome/complications , Pregnancy Complications/etiology , Diabetes, Gestational/etiology , Female , Humans , Hypertension, Pregnancy-Induced/etiology , Obstetric Labor, Premature/etiology , Pre-Eclampsia/etiology , Pregnancy , Risk FactorsABSTRACT
The objective of this work was to investigate the effect of orally administered evodiamine on the pharmacokinetics of dapoxetine and its active metabolite desmethyl dapoxetine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 10 mg/kg dapoxetine alone) and the combination group (10 mg/kg dapoxetine orally co-administered with 100 mg/kg evodiamine). The plasma concentration of dapoxetine and desmethyl dapoxetine were estimated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and different pharmacokinetic parameters were calculated using the Drug and Statistics 2.0 software. Compared to the control group, the pharmacokinetic parameter of t1/2, AUC(0-∞) and Tmax of dapoxetine in combination group was significantly increased by 63.3% (p < 0.01), 44.8% (p < 0.01) and 50.4% (p < 0.01), respectively. Moreover, evodiamine had significantly decreased the pharmacokinetic parameter of t1/2 and AUC(0-∞) of desmethyl dapoxetine. This study demonstrated that evodiamine inhibits the metabolism of dapoxetine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing dapoxetine to the patients already taking evodiamine.
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Benzylamines/pharmacokinetics , Naphthalenes/pharmacokinetics , Quinazolines/pharmacology , Animals , Area Under Curve , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Half-Life , Male , Plant Extracts , Rats , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
Background and purpose:Pathogenic gene polymorphism may affect the function of gene, leading to the difference of individual tumor susceptibility and heterogeneity of bioactive substances in individuals. The purpose of this study was to investigate the interrelationship betweenHER-2 gene polymorphism and its protein expression, and to evaluate their association with the clinicopathological characteristics of breast cancer.Methods:The data from a total number of 303 female breast cancer patients of Han ethnicity were collected. The MassARRAY platform was used to examineHER-2 gene rs2517954 and rs2517955 single nucleotide polymorphisms. Meanwhile immunohistochemistry was used to detect HER-2 protein expression and corresponding estrogen receptor (ER), progesterone receptor (PR), P53 and Ki-67 expressions in breast cancer tissues. Pearson chi-square test was used to study the relationship of the two loci and the protein expression, and their correlation with clinicopathological features of breast cancer was analyzed.Results:Under the codominant model,HER-2 gene rs2517954 and rs2517955 loci polymorphisms were associated with its protein expression (χ2=9.613,P=0.008;χ2=9.613,P=0.008). And under the dominant model,HER-2 gene rs2517955 loci TT homozygous and CT heterozygous mutant was associated with its protein expression (χ2=8.894,P=0.003). There were no signiifcant correlations betweenHER-2 gene rs2517954, and rs2517955 loci polymorphisms, and breast cancer patients’ clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki-67 and P53 expressions (P>0.05).Conclusion:HER-2 gene rs2517955 loci polymorphism is correlated with its protein expression. Further studies may be helpful to elucidate the mechanism of HER-2 protein expression in breast cancer.
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PURPOSE: This study was designed to assess the protein levels of transformation/transcription domain-associated protein (TRRAP) in invasive ductal breast carcinomas, and investigated the association between TRRAP and the clinicopathological features of breast cancer. METHODS: We examined TRRAP protein expression in 470 breast cancer tissues and normal breast tissues by tissue microarray to study the correlation between TRRAP expression and clinicopathological features. This was analyzed using the chi-square test. Kaplan-Meier survival curves and log-rank tests were applied to analyze the survival status. Cox regression was applied for multivariate analysis of prognosis. RESULTS: The data demonstrated that expression of TRRAP was significantly lower in breast carcinomas (36.6%) than in corresponding normal breast tissues (50.8%). In addition, TRRAP protein levels negatively correlated with tumor size, and indicated poor differentiation, increased nodal involvement, and low p53-positive rates. Analysis of survival revealed that lower TRRAP expression correlated with shorter survival time. Univariate analyses identified TRRAP and progesterone receptor as independent protective factors for breast cancer prognosis. However, Ki-67, tumor size, and nodal involvement appeared to be independent risk factors. CONCLUSION: The findings indicate a significant correlation between TRRAP protein levels and adverse prognosis in breast cancer. Therefore, TRRAP could be a prognostic biomarker for breast cancer. In addition, TRRAP is also a predictive biomarker of breast cancer treatment.
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Biomarkers , Breast Neoplasms , Breast , Kaplan-Meier Estimate , Multivariate Analysis , Prognosis , Receptors, Progesterone , Risk FactorsABSTRACT
Fibroblast growth factor receptor 3(FGFR3)plays important roles in cell proliferation,diffe rentiation,and angiogenesis.Recent studies have demonstrated that FGFR3 is associated with progression of breast cancer and has effects in endocrine therapy resistance breast cancer.It has also been showed that FGFR3 is correlated with breast cancer prognosis.
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Circulating cell-free DNA (cfDNA), which is released by normal cells and cancer cells, is defined as extracellular DNA in the blood. The cfDNA levels in breast cancer patients are higher than those in healthy control donors. cfDNA also carries the features of tumor tissue, such as mutations, methylations, copy number changes, and loss of heterozygosis. cfDNA is a potential bio-marker in the diagnosis, management, and prognosis of breast cancer. In this review, the authors briefly describe the biological features of cfDNA, and discuss its clinical utility as a blood biomarker in quantitative and qualitative research.
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As a heritable regulation , epigenetics can regulate gene expression by other ways without changing the DNA sequence ,and change cell or individual phenotypes .DNA methylation is an issue in the field of epigenetics research.Recently,many studies have been demonstrated that the methylation of repetitive DNA ,spe-cific gene and CpG island and loss of imprinting play an important role in tumor occurrence .As the development of technological approaches to DNA methylation ,we have a more comprehensive understanding on methylation pat-terns.As specific markers,abnormal methylation sites in the genome can be used in the diagnosis ,treatment and prognosis predictor of disease .For tumor development caused by DNA methylation ,the application of demethylat-ing drugs have achieved good effect in clinical treatment .
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Background and purpose:Breast cancer as one of the most common malignant tumor among women in China, it accounts for 12.2% of all newly diagnosed breast cancers and 9.6% of all deaths from breast cancer worldwide. The aim of this study was to investigate the relationship between single nucleotide polymorphisms(SNPs) in 2q35rs13387042and 8q24 rs13281615and the risk of breast cancer in Han premenopausal women of Northern China. Methods:280 patients with breast cancer and 287 healthy controls in premenopausal state were genotyped for SNP 2q35rs13387042and 8q24 rs13281615 by the SNaPshot method, and compared the different genotypes and alleles with relation to breast cancer risk.Results:Differences of 2q35 rs13387042 genotype frequencies between breast cancer and control were signiifcantly different (P=0.017). No statistically signiifcant difference of 8q24 rs13281615 genotype frequencies between breast cancers and controls was found (P=0.967). The results of logistic regression showed that the carriers of GA genotype and GA+ AA genotype increased risk for breast cancer compared to the carriers with 2q35 rs13387042 GG genotype(OR=1.793, 95%CI: 1.177-2.733,P=0.007;OR=1.691, 95%CI: 1.122-2.550,P=0.012), but not the carriers of AA genotype; Compared with G allele, A allele signiifcantly increased the risk of breast cancer(OR= 1.505, 95%CI: 1.033-2.193,P=0.033). The carriers of AG genotype or GG genotype or AG+GG genotype did not confer risk for breast cancer compared to the carriers with 8q24 rs13281615 AA genotype(OR=0.992, 95%CI: 0.660-1.490,P=0.968;OR=1.047, 95%CI: 0.642-1.708,P=0.853;OR=1.007, 95%CI: 0.682-1.487,P=0.971); Compared with A allele, G allele did not increase the risk of breast cancer(OR=1.021, 95%CI: 0.809-1.288,P=0.863).Conclusion:This experiment veriifed that 2q35 rs13387042 polymorphism site increased risk of breast cancer susceptibility among Han premenopausal women of Northern China. There was not any signiifcant association between 8q24 rs13281615 poly-morphism site and breast cancer susceptibility among Han premenopausal women of Northern China under the current sampling scale.
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The spindle assembly checkpoint ( SAC) is an important monitoring mechanism to monitor the connection between centromeres and microtubules and to ensure proper chromosome separation in human .Mitotic arrest defective protein(Mad)family,as an important part of SAC,plays a crucial role in the process of mitosis. Mutations or altered expressions of Mad may lead to abnormal separations of chromosomes and play a partial role in tumorigenesis ,poor prognosis and chemotherapy drug resistance .
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Objecive To explore the significance of RECK expression in breast cancer .Methods Im-munohistochemical staining was used to analyze RECK expression levels in patients with breast cancer .We com-pared these data with the clinicopathological features of these patients .Rseults Breast cancer patients with nega-tive RECK expression had significantly lower DFS and 5-year survival rates than patients with positive RECK expression.In addition,for node-negative breast cancer ,negative RECK expression indicated markedly unfavor -able survival rate than positive arm .Multivariate analysis further confirmed that RECK expression was an inde -pendent prognostic factor for patients with breast cancer .Conclusion The loss of RECK expression indicates un-favorable survival rate for patients with breast cancer .RECK expression is a new ,important risk factor for recur-rence in breast cancer .
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Hox genes encode a family of homeodomain-containing transcription factors that determine cellular identity during development and which are also expressed in some types of cancer. The HOXD3 gene, a member of the Hox gene family, has been demonstrated to be expressed in several tumor cell lines, which exhibit enhanced invasion and metastasis through coordinate expression of metastasis-associated factors. However, the clinical impact of HOXD3 in breast cancer remains unclear. In the current study, we examined the expression of HOXD3 and integrin ß3 by immunohistochemical staining in patients with invasive breast cancer. We found that HOXD3 expression was significantly frequent in high histopathological grade and hormone-receptor negative breast cancer patients. The expression of HOXD3 was closely associated with integrin ß3 expression. Furthermore, patients with high HOXD3 expression levels in their breast tumors had significantly shorter survival times than patients in which HOXD3 was weakly expressed in breast tumors. Univariate and multivariate analyses confirmed that increased HOXD3-expression was an independent and significant factor in predicting poor prognosis for patients with breast cancer. In conclusion, HOXD3 expression is a significant unfavorable prognostic factor for patients with invasive breast cancer and as such is a potentially useful prognostic marker for breast cancer.
