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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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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 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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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
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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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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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
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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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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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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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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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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FGFR2 plays an important role in cell proliferation and differentiation and FGFR2 gene has its own genetic polymorphism. It has recently been demonstrated that this genetic polymorphism is associated with risk of development of breast cancer and clinically pathological factors
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Objective To evaluate the safety and efficacy of neoadjuvant chemotherapy combined with PA-MSHA injection for the treatment of locally advanced breast cancer. Methods An open, randomized, controlled clinical trial was conducted in this study. 42 locally advanced breast cancer patients were randomly assigned to two groups, namely the experimental group (20 cases) and control group (22 cases). All the patients received chemotherapy of TEC regimen, while, in addition, the patients in experiment group received PA-MSHA injection. After the treatment, the efficacy of treatment was evaluated. The safety and tolerance of patients were also measured during the treatment. Results The overall response rate (CR+PR) [75.0 %(15/20)]in the experiment group was significant higher than that [54.6 %(12/22)]in control group (P < 0.01). Adverse reactions were found for 9 cases in experiment group, four of whom received medical care while the others recovered automatically. Conclusion PA-MSHA injection can significantly enhance the efficaey of neoadjuvant chemotherapy on the patients with locally advanced breast cancer. The PA-MSHA injection which has been proved safety in treatment is an ideal supplementary therapy for breast cancer.
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Objective To evaluate the association between the polymorphisms of BT-H4 gene and the risk of breast cancer, a case-control study was conducted in the population of Heilongjiang province, China. Methods We genotyped the single nucleotide polymorphisms of rs10754339, rs10801935 and rs3738414 in B7-H4 gene by PCR-RFLP in a Chinese population consisting of 287 breast cancer cases and 305 controls matched for age and sex, tagged all common haplotypes (frequency ≥ 1%), and analyzed the differences between patients and normal controls. Results Our data indicated that in rs10754339, the frequencies of G allele, AA genotype and AG genotype were significantly different between patients and controls (P=0.030, OR 1.359, 95 % CI 1.030-1.794; P=0.018, OR 0.671, 95 % CI 0.482-0.935; P=0.029, OR 1.455, 95 % CI 1.038-2.038, respectively). In rs3738414, the frequencies of A allele, GG genotype and AG genotype were significantly different between patients and controls (P=0.0008, OR 0.604, 95 % CI 0.455-0.803; P=0.001, OR 1.804, 95 % CI 1.289-2.253; P=0.005, OR 0.612, 95 % CI 0.435-0.862). The frequencies of AAA haplotype and GAG haplotype were significantly different between patients and controls (P=0.0015, OR 0.614, 95 % CI 0.456-0.828; P=0.0003, OR 1.954, 95 % CI 1.363-2.803). Conclusion Polymorphisms of B7-H4 gene appear to be associated with breast cancer in the population of Heilongjiang province, China.
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<p><b>OBJECTIVE</b>To detect the serum proteomic patterns in breast cancer patients by surface enhanced laser desorption/ionization time of flight (SELDI-TOF-MS) protein chip array techniques, to screen biomarker candidates and build diagnostic models in order to evaluate their clinical significance.</p><p><b>METHODS</b>SELDI-TOF-MS technique and weak cation exchanger (WCX2) protein chip were used to detect the serum proteomic patterns of 38 patients with breast cancer, 33 patients with benign breast diseases and 43 normal control subjects. Biomarker Wizard 3.01 and Biomarker Pattern Software 5.01 were used in combination to analyze the data and to develop diagnostic models.</p><p><b>RESULTS</b>Four protein peaks pattern (M2077_07, M1827_38, M2650_51 and M2060_62 mass/charge ratio [m/z]) was observed in the model I, and it could be used to distinguish breast cancer from non cancerous diseases. Its sensitivity and specificity were 73.7% (28/38) and 73.7% (56/76), respectively. The model II was formed by 5 protein peaks (M2251_62, M3405_56, M3428_16, M4666_98, M16239_8 m/z). When it was used in differential diagnosis between stage I breast cancer and benign breast diseases, the sensitivity and specificity were 84.8% (28/33) and 55.6% (5/9), respectively. Another 5 peaks (M1701_48, M3116_17, M1676_88, M5890_33, M2921_02 m/z) could build the model III to distinguish stage I and stage II approximately IV breast cancers. Its sensitivity and specificity were 88.9% (8/9) and 86.2% (25/29), respectively.</p><p><b>CONCLUSION</b>Our findings suggested that application of SELDI-TOF-MS can be of great potential for early breast cancer screening, diagnosis and preoperative staging, and deserves further studies.</p>