Effects of FGFR1 Gene Polymorphisms on the Risk of Breast Cancer and FGFR1 Protein Expression.

BACKGROUND/AIMS: Fibroblast growth factor receptor 1 (FGFR1) is widely considered to play an important role in mammary carcinogenesis. Some common variants in FGFR1 might be associated with its expression, and further affect breast cancer risk. The aim of this study was to investigate effects of single-nucleotide polymorphisms (SNPs) in FGFR1 on breast cancer susceptibility and FGFR1 protein expression. METHODS: SNPs rs17182023, rs17175624 and rs10958704 in FGFR1 were genotyped in 747 breast cancer cases and 716 healthy controls by SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. Immunohistochemistry(IHC) was used to detect FGFR1 protein expression, and the association of FGFR1 polymorphisms with its protein expression was analyzed by Pearson's chi-square test. Additionally, Cox regression and Kaplan-Meier analysis was used to evaluate the association between FGFR1 protein expression and breast cancer prognosis. RESULTS: The minor allele of rs17182023 in FGFR1 was significantly associated with reduced breast cancer risk, with an odds ratio of 0.800 (95%CI = 0.684-0.935). No significant associations were detected between other SNPs and breast cancer. Moreover, rs17182023 was correlated to FGFR1 protein expression (P = 0.006), and patients with high FGFR1 protein expression tended to have poor outcomes. CONCLUSIONS: SNP rs17182023 was correlated to reduced breast cancer risk, and was associated with FGFR1 protein expression. High FGFR1 protein expression was an independent risk factor of breast cancer, and resulted in poor prognosis.

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer.

Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and FGFR4 polymorphisms have been implicated in both normal development and cancer, including breast cancer. In the present study, we investigated correlations between polymorphisms in FGFR4 and breast cancer prognosis. The FGFR4 SNPs rs1966265 and rs351855 were genotyped in 747 breast cancer patients using the SNaPshot method. FGFR4 protein expression was detected by immunohistochemistry in 339 samples. SNP rs351855 was correlated with FGFR4 protein expression under dominant and co-dominant models. Lymph node metastasis (LNM), ER (estrogen receptor) status, and molecular subtype were associated with high FGFR4 expression. Univariate analysis revealed rs351855 (CC/CT: P = 0.027, CC/TT: P < 0.001, CC/CT + TT: P = 0.005) to be a prognostic predictor, and multivariate analysis indicated rs351855 (CC/TT: P = 0.005) to be an independent prognostic factor. Kaplan-Meier survival analysis showed that high FGFR4 protein expression was associated with a poor prognosis. SNP rs351855 was correlated with worse outcomes, with a dose-dependent effect. The results of this study show that FGFR4 SNP rs351855 is associated with up-regulation of FGFR4 protein expression and a worse prognosis in breast cancer.

Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit ß-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.

BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/ß-catenin signaling and inhibited the growth of AR+/ER- breast cancer. CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

Superomniphobic, transparent, and antireflection surfaces based on hierarchical nanostructures.

Optical surfaces that can repel both water and oil have much potential for applications in a diverse array of technologies including self-cleaning solar panels, anti-icing windows and windshields for automobiles and aircrafts, low-drag surfaces, and antismudge touch screens. By exploiting a hierarchical geometry made of two-tier nanostructures, primary nanopillars of length scale ∼ 100-200 nm superposed with secondary branching nanostructures made of nanoparticles of length scale ∼ 10-30 nm, we have achieved static contact angles of more than 170° and 160° for water and oil, respectively, while the sliding angles were lower than 4°. At the same time, with respect to the initial flat bare glass, the nanotextured surface presented significantly reduced reflection (<0.5%), increased transmission (93.8% average over the 400 to 700 nm wavelength range), and very low scattering values (about 1% haze). To the authors' knowledge, these are the highest optical performances in conjunction with superomniphobicity reported to date in the literature. The primary nanopillars are monolithically integrated in the glass surface using lithography-free metal dewetting followed by reactive ion etching,1 while the smaller and higher surface area branching structure made of secondary nanoparticles are deposited by the NanoSpray2 combustion chemical vapor deposition (CCVD).

Association between single nucleotide polymorphisms in the OPRM1 gene and intraoperative remifentanil consumption in northern Chinese women.

BACKGROUND: Recent studies have suggested that some single nucleotide polymorphisms (SNPs) in the human µ-opioid receptor gene (OPRM1) affect the postoperative analgesic efficacy of opioids and their side effects. In this study, we assessed the association between SNPs in the OPRM1 gene and intraoperative remifentanil consumption as well as perioperative side effects during gynecological hysteroscopic surgery in women from Northern China. METHODS: We analyzed 178 women undergoing gynecological hysteroscopic surgery. SNP genotyping was performed using the SNaPshot method. The state anxiety index (SAI) and pressure pain threshold (PPT) of all patients were assessed preoperatively. Monitored anesthesia care was maintained by the intravenous infusion of remifentanil. Intraoperative remifentanil usage and perioperative side effects were recorded. Statistical analyses were performed using SPSS software. RESULTS: Patients carrying one or two copies of the minor allele (G allele) of rs558025 required significantly more intraoperative remifentanil than patients without the minor allele (p = 0.001, corrected p = 0.006). There were no significant associations between the six SNPs and various clinical characteristics. No significant associations between the six SNPs and PPT or SAI were found in our study. CONCLUSIONS: SNP rs558025 in the OPRM1 gene was associated with intraoperative remifentanil consumption during gynecological hysteroscopic surgery in our subjects.

A flexible and stretchable triboelectric nanogenerator based on a medical conductive hydrogel for biomechanical energy harvesting and electronic switches.

With the development of intelligent wearable electronic products, new requirements are put forward for large-scale production and durable power supplies and sensors. Herein, a flexible and stretchable single-electrode triboelectric nanogenerator (TENG) based on a medical conductive hydrogel (MCH) has been fabricated for biomechanical energy harvesting and electronic switches. The obtained MCH-TENG encapsulated by silicone rubber as an electrification layer demonstrated high electrical output performances. The size of the fabricated MCH-TENG was 40 × 60 mm2, which can generate an open-circuit voltage of 400 V, a power density of 444.44 mW m-2, and power 240 LEDs in series at a contact frequency of 3.0 Hz. The device can act not only as a power supply to drive electronic devices, but also as an energy collector to collect the energy of human movements. Particularly, as an electronic switch, the device enabled a high current amplification through the Darlington transistor circuit. Consequently, this work provides a new perspective of flexible and stretchable MCH-TENGs for wearable electronic devices.

Increased expression of fibroblastic growth factor receptor 2 is correlated with poor prognosis in patients with breast cancer.

BACKGROUND AND OBJECTIVES: Although there is growing evidence supporting the hypothesis that fibroblast growth factor receptor 2 (FGFR2) is one of the few candidate genes linked with breast cancer susceptibility, the precise role of FGFR2 protein expression in breast cancer is still unknown. Our study examines FGFR2 protein expression in breast cancer and determines its associations with clinicopathological features and survival. METHODS: Specimens from 125 invasive ductal carcinoma grade 2 (IDC2) breast cancer patients were investigated by immunohistochemistry for FGFR2 protein expression. Associations between the expression of FGFR2 and various clinicopathological features as well as survival status were studied. RESULT: Cytoplasmic and nuclear FGFR2 were expressed in 64.8% and 56.8% of breast cancer patients, respectively. Cytoplasmic FGFR2 expression was significantly associated with tumor size and TNM stage. Furthermore, patients with high expression levels of cytoplasmic and nuclear FGFR2 showed much lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low FGFR2 expression. Cytoplasmic FGFR2 expression and lymph node metastasis were independent prognostic factors for both DFS and OS by multivariate analysis. CONCLUSIONS: High FGFR2 expression is correlated with poor OS and DFS in breast cancer patients. It could be a biomarker for poor prognosis.

Risk of genome-wide association study newly identified genetic variants for breast cancer in Chinese women of Heilongjiang Province.

Recent genome-wide association studies have identified seven single nucleotide polymorphisms (SNPs) associated with breast cancer, but mainly in Europeans. In this study, the authors evaluated the effect of these loci on breast cancer and its disease characteristics in women from northeast of China, Heilongjiang Province. Seven SNPs were successfully genotyped in 492 breast cancer patients and 510 healthy controls using the SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations between SNPs and disease characteristics were examined by the chi-square test or one-way ANOVA as needed. The authors confirmed the effects of the allele A for rs2046210 at 6q25 on increased breast cancer risk in the population, with odds ratio 1.417 (P = 2×10⁻4). However, no significant association was detected between SNPs from TNCR9, LSP1, MAP3K1, 2q35, and 8q24 and breast cancer. Analyses of the disease characteristics showed that SNP rs2046210 was associated with age at menopause (P = 0.001). MAP3K1 SNP rs889312 and LSP1 SNP rs3817198 were associated with HER2 status in the patient cohort (P = 0.036 and P = 0.005, respectively). And SNP rs3817198 was also associated with the combined status of estrogen receptor, progesterone receptor, and HER2 (P = 0.012). SNP rs13281615 was associated with age at menarche (P = 0.023), and SNP rs3803662 was associated with average duration of breastfeeding (P = 0.036). All other disease characteristics, including tumor grade, clinical stage, and the status of estrogen receptor or P53, were not significantly associated with any of these variants. These results suggested that the rs2046210 was associated with breast cancer in a Northern Chinese population, and some SNPs were also associated with breast cancer characteristics.

Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-κB-VCAM-1 Signaling Pathway.

OBJECTIVES: Complement 1q binding protein (C1QBP/HABP1/p32/gC1qR) has been found to be overexpressed in triple-negative breast cancer (TNBC). However, the underlying mechanisms of high C1QBP expression and its role in TNBC remain largely unclear. Hypoxia is a tumor-associated microenvironment that promotes metastasis and paclitaxel (PTX) chemoresistance in tumor cells. In this study, we aimed to assess C1QBP expression and explore its role in hypoxia-related metastasis and chemoresistance in TNBC. MATERIALS AND METHODS: RNA-sequencing of TNBC cells under hypoxia was performed to identify C1QBP. The effect of hypoxia inducible factor 1 subunit alpha (HIF-1α) on C1QBP expression was investigated using chromatin immunoprecipitation (ChIP) assay. The role of C1QBP in mediating metastasis, chemoresistance to PTX, and regulation of metastasis-linked vascular cell adhesion molecule 1 (VCAM-1) expression were studied using in vitro and in vivo experiments. Clinical tissue microarrays were used to verify the correlation of C1QBP with the expression of HIF-1α, VCAM-1, and RELA proto-oncogene nuclear factor-kappa B subunit (P65). RESULTS: We found that hypoxia-induced HIF-1α upregulated C1QBP. The inhibition of C1QBP notably blocked metastasis of TNBC cells and increased their sensitivity to PTX under hypoxic conditions. Depletion of C1QBP decreased VCAM-1 expression by reducing the amount of P65 in the nucleus and suppressed the activation of hypoxia-induced protein kinase C-nuclear factor-kappa B (PKC-NF-κB) signaling.immunohistochemistry (IHC) staining of the tissue microarray showed positive correlations between the C1QBP level and those of HIF-1α, P65, and VCAM-1. CONCLUSION: Targeting C1QBP along with PTX treatment might be a potential treatment for TNBC patients.

Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer.

Objective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC. Methods: After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined in vitro by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis. Results: We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines. Conclusion: Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.

Circulating cell-free DNA-based methylation patterns for breast cancer diagnosis.

Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54-99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56-100%), and AUPRC = 0.9220 (95% CI: 91.02-94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72-99.27%), and AUPRC = 0.9111 (95% CI: 88.45-93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07-98.91%), and AUPRC = 0.8640 (95% CI: 82.82-89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72-97.87%) and a specificity of 98.70% (95% CI: 86.36-100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75-99.55%), and AUPRC = 0.9800 (95% CI: 96.6-99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95-96.34%), and AUPRC = 0.9490 (95% CI: 91.7-98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.

Fibroblast growth factor receptor 4 as a prognostic indicator in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) constitutes up to 15% of all breast cancers. It is one of the most aggressive breast cancers and is more prone to metastasize compared with other subtypes. Breast cancer patients with this subtype usually have a poor prognosis. Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and early analyses identified that FGFR4 was involved in breast cancer. However, the prognostic effect of FGFR4 on TNBC is unknown. In the present study, we investigated the association between FGFR4 and TNBC prognosis. METHODS: A total of 282 TNBC patients were enrolled. FGFR4 protein expression was detected in these 282 TNBC patients using immunohistochemistry (IHC). RESULTS: In the present study, FGFR4 was highly expressed in TNBC patients. Lymph node metastasis (LNM) (P=0.033) and p53 status (P=0.019) were associated with high FGFR4 expression. Univariate analysis identified high FGFR4 expression (P=0.016) as a prognostic predictor, and multivariate analysis found that high FGFR4 expression (P=0.016) was an independent prognostic factor. The Kaplan-Meier survival curve showed that high FGFR4 protein expression was correlated with poorer overall survival (OS). CONCLUSIONS: The results of our present study show that FGFR4 protein expression is correlated with a worse prognosis in TNBC.

(Z)-2-Acetamido-3-(4-chloro-phen-yl)acrylic acid.

In the title compound, C(11)H(10)ClNO(3), the mol-ecule consists of a benzene ring and an acetamido-acrylic acid unit on opposite sides of the C=C double bond. In the crystal, inter-molecular O-H⋯O and N-H⋯O hydrogen bonds assemble the mol-ecules into infinite two-dimensional ribbons. These ribbons are linked into a network by inter-molecular C-H⋯π contacts.

(Z)-2-Hydr-oxy-3-(4-methoxy-phen-yl)acrylic acid.

In the structure of the title compound, C(10)H(10)O(4), inversion dimers linked by pairs of O-H⋯O hydrogen bonds link the carboxylic acid groups. Further O-H⋯O links cross-link the dimers into sheets running along the b-axis direction.

Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.

PURPOSE: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. RESULTS: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. CONCLUSIONS: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

To tell or not to tell: attitudes of Chinese oncology nurses towards truth telling of cancer diagnosis.

AIMS AND OBJECTIVES: To investigate the attitude of oncology nurses towards whether and how to disclose diagnoses to patients with early-stage cancer or terminal illness. BACKGROUND: The attitudes of patients and doctors towards the disclosure of cancer diagnosis differed from culture to culture. However, little research has focused on the attitudes of Chinese oncology nurses. DESIGN: Survey. METHODS: A questionnaire investigating nurses' attitudes towards truth telling was delivered to 243 Chinese oncology nurses. RESULTS: One hundred and ninety-nine (819%) nurses completed the questionnaire. 814% of the nurses reported that patients with early-stage cancer should be informed of the diagnosis, while only 442% believed that patients with terminal illnesses should know the truth (p < 0001). Nurses who preferred truth telling reported that patients with early or terminal stages of cancer should be informed by the doctor in charge (765% vs. 739%, respectively; p > 005), immediately after the diagnosis (759% vs. 795%, respectively) and in a quiet and undisturbed room (809% vs. 705%, respectively; p > 005). Nurses' attitudes towards truth telling of terminal cancer were influenced by their educational level and work experience. CONCLUSION: Oncology nurses differed in their attitudes towards truth telling of different stages of cancer. Nurses who preferred disclosure reported that cancer patients should be informed by the doctor in charge immediately after the diagnosis and in a quiet and undisturbed room. RELEVANCE TO CLINICAL PRACTICE: Many Chinese doctors, patients and their relatives believed that patients with terminal illness should not know their diagnosis. Thus, oncology nurses need additional training to deal with these situations.

The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China.

BACKGROUND: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. RESULTS: Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively). MATERIALS AND METHODS: Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. CONCLUSIONS: CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma.

Increased breast cancer risk with HABP1/p32/gC1qR genetic polymorphism rs2285747 and its upregulation in northern Chinese women.

OBJECT: Hyaluronic acid binding protein 1 (HABP1/p32/gC1qR) is overexpressed in breast cancer. However, it is unknown whether HABP1 gene polymorphisms affect breast cancer risk. This study aims to evaluate the potential association of single nucleotide polymorphisms (SNPs) of HABP1 with breast cancer in northern Chinese women. RESULTS: The minor allele of rs2285747 was strongly associated with breast cancer with OR of 1.553 (95% CI = 1.251-1.927). SNP rs2285747 was also associated with high HABP1 protein expression under the co-dominant and dominant model (p = 0.005, p = 0.019, respectively). For rs2472614, the patients with CG and GG were more likely to have HER2 negative tumors compared to CC (p = 0.015). For rs3786054, the patients with AG and GG were more likely to have HER2 and P53 negative breast cancer compared to AA (p = 0.024, p = 0.064, receptively). MATERIALS AND METHODS: Seven SNPs were analyzed in 505 breast cancer patients and 505 controls using SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations of SNPs with HABP1 protein expression and disease characteristics were examined by chi-square test. CONCLUSIONS: SNP rs2285747 of HABP1 increased breast cancer risk and elevated its protein expression in northern Chinese women.

A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer.

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.

Effects of HER2 genetic polymorphisms on its protein expression in breast cancer.

BACKGROUND AND PURPOSES: HER2 protein expression has been considered to be an important prognostic factor in breast cancer patients. Although the molecular mechanism of HER2 protein expression is currently unknown, single nucleotide polymorphisms (SNPs) of the HER2 gene may have some effects on its own expression. Here, we performed a trial to study the association between HER2 genetic polymorphisms and its protein expression in breast cancer. METHODS: Three SNPs in the HER2 gene were genotyped in 303 breast cancer patients using the Sequenom Mass ARRAY system. HER2 protein expression, ER, PR, P53, and Ki67 status was detected by immunohistochemistry. A Pearson's chi-square test was used to analyze the associations of the polymorphisms with its protein expression, corresponding with clinicopathological characteristics of breast cancer. RESULTS: Under the codominant model, rs1058808 and rs2517956 polymorphisms were associated with HER2 protein expression in breast cancer (p=0.007; p=0.008, respectively). For SNP rs1058808, patients with genotypes CG and GG were more likely to have high HER2 protein expression than patients with genotype CC (p=0.007). No significant associations could be found between the three SNPs and breast cancer patients' clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki67 and P53 status (p>0.05). CONCLUSIONS: HER2 rs1058808 and rs2517956 polymorphisms are associated with its protein expression in breast cancer. Our study might provide new insights into the mechanisms of HER2 protein expression.