Decoupling of gray and white matter functional networks in cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.

Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol.

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular hydride transfer reactions of alkylamines under mild conditions. Besides transformations of small molecules, these reactions enable unique late-stage modification of complex peptides. Mechanistic investigations uncover that the key to these intermolecular hydride transfer processes lies in the accommodating conformation of solvent-mediated macrocyclic transition states, where the aggregates of HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between the lone electron pair of nitrogen and the antibonding orbital of amine's α C-H bond plays a critical role in the C-H activation, promoting its hydride liberation.

Artificial Intelligence Imaging for Predicting High-risk Molecular Markers of Gliomas.

Gliomas, the most prevalent primary malignant tumors of the central nervous system, present significant challenges in diagnosis and prognosis. The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) published in 2021, has emphasized the role of high-risk molecular markers in gliomas. These markers are crucial for enhancing glioma grading and influencing survival and prognosis. Noninvasive prediction of these high-risk molecular markers is vital. Genetic testing after biopsy, the current standard for determining molecular type, is invasive and time-consuming. Magnetic resonance imaging (MRI) offers a non-invasive alternative, providing structural and functional insights into gliomas. Advanced MRI methods can potentially reflect the pathological characteristics associated with glioma molecular markers; however, they struggle to fully represent gliomas' high heterogeneity. Artificial intelligence (AI) imaging, capable of processing vast medical image datasets, can extract critical molecular information. AI imaging thus emerges as a noninvasive and efficient method for identifying high-risk molecular markers in gliomas, a recent focus of research. This review presents a comprehensive analysis of AI imaging's role in predicting glioma high-risk molecular markers, highlighting challenges and future directions.

Preoperative Radiotherapy Does Not Change the Existing Treatment Paradigm in Stage III Breast Cancer.

INTRODUCTION: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). METHODS: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. RESULTS: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288-2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096-1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010-1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127-1.906, p = 0.004). CONCLUSION: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer.

Clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy.

OBJECTIVE: The present study aimed to evaluate the clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: Patients with HER2 negative breast cancer receiving NAC from January 2017 to December 2020 were enrolled in this study. The clinicopathological characteristics, response to NAC, evolution of HER2 and prognostic value were retrospectively analyzed. RESULTS: 410 patients were included. The proportion of HR positive disease in HER2-low cases was higher than in HER2-zero population (75.8 % vs. 65.8 %, P = 0.040). No statistical significant difference in pCR rate was observed between HER2-low and HER2-zero patients (33.8 % vs. 39.3 %, P = 0.290) when pCR was defined as ypTis/0ypN0. Exploratory analysis revealed that the pCR rate of HER2-low cases was significantly lower than HER2-zero patients in the entire population (19.8 % vs. 33.3 %, P = 0.004) and HR positive population (12.6 % vs. 29.9 %, P = 0.001) when pCR was defined as ypT0ypN0. The evolution rate of HER2 expression after NAC was 31.0 % in HER2-zero patients and 24.7 % in HER2-low patients. Compared with patients with HR positive disease, patients with TNBC had higher evolution rate of HER2 expression after NAC (37.7 % vs. 23.6 %). Significant association was observed between HER2 evolution with histology type and Ki-67 index in HER2-zero patients and with lymph node involvement, HR status and Ki-67 index in HER2-low patients. Prognostic impact of HER2 evolution was not observed. CONCLUSIONS: HR positive and HR negative HER2-low breast cancer exhibit different clinicopathological features, response to NAC and HER2 evolution after treatment.

Brain metastasis in de novo stage IV breast cancer.

OBJECTIVES: Information of brain metastasis (BM) in de novo stage IV breast cancer is lacking, which is an unavoidable problem and dilemma in practice. Understanding the current situation is helpful for the clinical cognition and decision-making. METHODS: We retrospectively analyzed the clinical and survival information of de novo stage IV breast cancer with BM between 2015 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression analyses were performed to identify predictors of BM and factors associated with all-cause mortality in de novo stage IV breast cancer, respectively. Overall survival (OS) was calculated using Kaplan-Meier and log-rank tests. RESULTS: Our cohort consisted of 1366 patients with BM in de novo stage IV breast cancer, with an incidence of 8.38% in patients with metastatic disease to any distant site. Incidence was highest among patients with metastatic disease with HR-HER2+ (12.95%) and HR-HER2- (13.40%) subtypes. The higher the number of extracranial metastases, the higher the BM incidence. The median OS was 12.0 (95%CI: 10.426-13.574) months in BM group; it was longest in HR + HER2+ (19.0[95%CI: 11.793-26.207] months), and shortest in HR-HER2- (7.0 [95%CI:5.354-8.646] months). Marital status, subtype, and abundance of metastatic sites influenced morbidity and OS of BM in de novo stage IV breast cancer. CONCLUSIONS: Population-based estimates of the incidence and prognosis for patients with BM in de novo stage IV breast cancer were closely associated with subtype and metastatic burden. These findings may be helpful in developing diagnostic strategies, especially for brain screening.

HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study.

Background: There is accumulating evidence support human epidermal growth factor receptor 2 (HER2)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether HER2-low expression will affect the clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitor for patients with hormone receptor (HR)-positive, HER-2 negative metastatic breast cancer. Methods: Patients with HR+/HER2- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. HER2-zero was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/fluorescence in situ hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety. Results: 45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 HER-2-zero and 21 HER-2-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between HER-2-zero and HER-2-low patients. And simultaneously, HER2-zero and HER2-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively. Conclusions: HER2-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating HER2-low into systemic therapy decisions for patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitor.

Clinical, Pathological Complete Response, and Prognosis Characteristics of HER2-Low Breast Cancer in the Neoadjuvant Chemotherapy Setting: A Retrospective Analysis.

BACKGROUND: The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. METHODS: Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative. RESULTS: Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. CONCLUSIONS: HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer.

Background: Antiangiogenic agents provides an optional treatment strategy for patients with metastatic breast cancer. The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with HER-2 negative metastatic breast cancer. Methods: Patients with HER-2 negative metastatic breast cancer who have failed from prior therapy and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2018 to December 2020 were retrospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: 47 patients with HER-2 negative metastatic breast cancer received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 10 patients achieved PR, 25 patients had SD and 12 patients had PD. The overall ORR and DCR were 21.3% and 74.5%, respectively. Subgroup analysis suggested that there were no statistically significant differences in ORR and DCR with respect to HR status (positive vs. negative), treatment programs (monotherapy vs. combination) and treatment type in combination group (chemotherapy vs. immunotherapy). The patients who did not received previously anti-angiogenesis therapy had superior DCR (84.8% vs. 50.0%, P=0.012). Median PFS and OS were 5.0 months (95% CI=4.3-5.7) and 21.0 (95% CI=14.9-27.1) months, respectively. The PFS (6.5m vs. 3.5m, P=0.042)and OS (28.2m vs. 12.6m, P=0.040) were better in HR positive patients than HR negative patients. And simultaneously, patients who received anlotinib combination therapy obtained better PFS (5.5m vs. 3.0m, P=0.045). The incidence of Grade 3-4 adverse events(AEs) was 31.9%. Conclusions: Anlotinib monotherapy or combination therapy provide a viable third-line or above therapeutic strategy in patients with HER-2 negative metastatic breast cancer, a median PFS of 5.0 months was obtained with well tolerated toxicity.

lncRNA PCNAP1 predicts poor prognosis in breast cancer and promotes cancer metastasis via miR­340­5p­dependent upregulation of SOX4.

The high metastatic rate of breast cancer is the significant cause of its poor prognosis. The long noncoding RNA (lncRNA) proliferating cell nuclear antigen pseudogene 1 (PCNAP1) plays important roles in the initiation and progression of cancers; however, its regulatory function and molecular mechanism in breast cancer metastasis remains unknown. Therefore, we investigated the roles of lncRNA PCNAP1 in breast cancer metastasis by modulating the microRNA (miR)­340­5p/SOX4 axis using quantitative real­time PCR, in vivo mouse models, nucleo­cytoplasmic separation, western blot analysis, scratch assays, Transwell assays, luciferase reporter assays and MS2­RIP, in vitro and in vivo. lncRNA PCNAP1 was found to be upregulated in human breast cancer tissues, and high lncRNA PCNAP1 levels predicted poor overall survival. Function assays showed that knockdown of lncRNA PCNAP1 suppressed the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, lncRNA PCNAP1 functioned as a competing endogenous (ce)RNA for miR­340­5p to facilitate the expression of its target gene SRY­box transcription factor 4 (SOX4), promoting migration and invasion of breast cancer cells. Overall, we found that lncRNA PCNAP1 predicted a poor prognosis in breast cancer and promoted cancer metastasis via miR­340­5p­dependent upregulation of SOX4 expression. These results suggest that lncRNA PCNAP1 has potential as an alternative therapeutic target to suppress breast cancer metastasis.

Relationships between SNPs and prognosis of breast cancer and pathogenic mechanism.

BACKGROUND: Association between several single-nucleotide polymorphisms (SNPs) and breast cancer risk has been identified through genome-wide association studies (GWAS), but little is known about their significance in patients' prognosis. We screened SNPs which were related to the prognosis of breast cancer in Henan Han population, analyzed relevant genes by bioinformatics in database, and further constructed the genetic regulatory network involved in the pathogenesis of breast cancer. METHODS: We evaluated five SNPs in 232 cases of breast cancer at the Affiliated Tumor Hospital of Zhengzhou University. Relationships between five SNPs, clinical prognostic indicators, and disease-free survival (DFS) were evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of genes and Genome (KEGG) analysis were carried out to preliminarily establish genetic regulation network model of breast cancer. Bayesian algorithm was used to optimize the model. RESULTS: The multivariate Cox proportional hazards model confirmed that SNP rs3803662 (TOX3/TNRC9) had correlation with DFS independently. In the multivariate Cox proportional hazards model, compared with GA/AA, GG increased the recurrent risk of breast cancer (p = .021, hazard ratio [HR] = 2.914). GO analysis showed that the function of TOX3/TNRC9 included biological_process, molecular_function, and cellular_component. According to KEGG signaling pathway database, the map of breast cancer-related gene regulatory network was obtained. IGF-IGF1R-PI3K-Akt-mTOR-S6K was the best possible pathway for the differentiation of breast cancer cells in this network and ER-TOX3/TNRC9 was the best possible pathway for the survival of tumor cells in this network by Bayesian theorem optimization. CONCLUSIONS: SNP rs3803662 (TOX3/TNRC9) is an independent prognostic factor for breast cancer in Henan Han Population. ER-TOX3/TNRC9 is the best possible pathway involved in the pathogenesis of breast cancer.

Serum ATX as a novel biomarker for breast cancer.

Recent accumulating evidence indicates the biological actions of Autotaxin-Lysophosphatidic acid (ATX-LPA) signaling axis in malignant tumors. However, the role of Autotaxin-Lysophosphatidic acid signaling axis in breast cancer has not been reported. The present study aims to examine the alterations of serum autotaxin in breast cancer and discuss whether serum autotaxin could be useful as a novel parameter of breast cancer.Serum autotaxin antigen was measured in 112 patients with breast cancer and 50 healthy volunteers by ELISA. The association of serum autotaxin antigen levels with clinicopathological parameters and outcomes of breast cancer was analyzed.Serum autotaxin antigen was significantly higher in breast cancer patients than healthy volunteers (291.32 ±â€Š38.02 ng/ml vs 254.04 ±â€Š21.03 ng/ml, respectively; P < .0001). Serum autotaxin measurement successfully discriminated breast cancer patients from normal and healthy controls (AUC = 0.798, 95% CI: 0.732-0.864) with an optimal cut-off value of 267.34 ng/ml (sensitivity = 0.741, specificity = 0.800). Increased serum autotaxin was associated with breast cancer nodal status (P = .007), Tumor-Node- Metastasis (TNM) stage (P = .009) and Ki-67 index (P = .004). Univariate and multivariate Cox regression analysis revealed that elevated serum autotaxin showed an independent prognostic value for poor Disease-free survival.Our present study confirmed the elevation, potential diagnostic, and independent prognostic value of serum autotaxin for breast cancer. Serum autotaxin could serve as a reliable novel biomarker for breast cancer.

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

Magnetic resonance imaging patterns of tumor regression in breast cancer patients after neo-adjuvant chemotherapy, and an analysis of the influencing factors.

The objective of this study was to analyze the patterns of breast tumor shrinkage in patients after neo-adjuvant chemotherapy (NAC) based on magnetic resonance imaging (MRI), and to evaluate the influential factors. Preoperative breast dynamic contrast-enhanced MRI was performed on 88 patients before NAC, every 2 weeks during their chemotherapy treatment, and the week before their surgery. The MRI enhancement pattern of the primary tumors was classified into one of four categories based on BI-RADS-MRI: type I (postcontrast mass image), II (multiple small masses image), III (postcontrast mass image with peripheral non-mass enhancement image), and IV (nonmass enhancement image). Multivariate regression and χ2 test analyses were employed to establish significant associations. Two kinds of tumor regression patterns were observed: concentric shrinkage was observed in 39 lesions of 88 patients (44.3%), and nests or dendritic shrinkage was observed for the other 49 lesions (55.7%). ER+/HER2-, HER2+, and type I lesions were observed in 23 (62.2%), 21 (63.6%), and 29 (60.0%) patients, respectively, out of 49 nest or dendritic shrinkage pattern lesions. Triple negative breast cancer lesions, and type II, III, and IV lesions were observed in 13 (72.2%), 9 (81.8%), 10 (62.5%), and 10 (76.9%) patients, respectively, out of 39 lesions with a concentric shrinkage pattern. Molecular subtypes (χ2 =7.171, P<.05) and the MRI schedule of enhancement (χ2 =11.244, P<.05) were significantly associated with the tumor regression patterns. Multivariate analysis showed molecular subtypes (P<.05) and MRI pattern enhancement (P<.05) were significant predictive factors. Molecular subtypes and the MRI enhancement patterns of the primary tumors were significant predictive factors for tumor regression patterns of breast cancer after NAC.

Relationship between five GWAS-identified single nucleotide polymorphisms and female breast cancer in the Chinese Han population.

With the development of genome-wide association study (GWAS), an increasing number of genetic variables have been confirmed to be associated with breast cancer. Furthermore, an increasing number of studies from Asian populations are becoming available. Few GWAS loci have been replicated in the Chinese Han population. In a case-control study of breast cancer in the Henan Tumor Hospital (253 cases/339 controls), we evaluated five SNPs from GWAS of populations of European or Asian ancestry. In order to evaluate the contribution of genetic factors to population differences in breast cancer subtypes, all cases are defined by estrogen (ER), progesterone (PR) receptor, Human epidermal growth factor receptor - 2 (HER2), and Ki67 status. Different genotypes of rs3803662 (TOX3)/ (TNRC9)) in the case group and the control group are statistically significant (P = 0.044), but the ones of rs10069690 (TERT), rs2046210 (6q25.1), rs2981582 (EGFR2), and rs889312 (MAP3K1) have no significant statistical differences with breast cancer (P = 0.772, 0.308, 0.376, 0.468). The allelic frequencies of rs3803662 between the case group and the control group differ in recessive genetic models (odds ratio (OR) = 2.04, 95 % confidence interval (CI) 1.14-3.66) and in con-dominant inheritance models (OR = 2.17, 95 % CI 1.18-4.00). Compared with AA and GA, GG increased the risk of breast cancer (P = 0.017, 0.013). The genotype of rs2046210 (6q25.1), rs2981582 (EGFR2), rs889312 (MAP3K1), and rs3803662 (TOX3/TNRC9) has no statistical differences in different subtypes of breast cancer. Five common breast cancer susceptibility loci from GWAS are not strongly associated with breast cancer risk among the Han Chinese of the Henan province; only rs3803662 (TOX3/TNRC9) is confirmed to increase the risk of breast cancer. The different genotypes of five loci distribute equally in different subtypes of breast cancer.

[Associations between TOX3 rs3803662 polymorphisms and immunological markers of breast cancer].

OBJECTIVE: TOX3 gene was considered to be breast cancer susceptibility gene in the European population and East Asian populations. This study was aimed to investigate the relevance of TOX3 gene rs3803662 single nucleotide polymorphisms and sporadic breast cancer susceptibility among the Han Nationality in Henan Province. METHODS: A case-control study was performed among 253 patients with sporadic breast cancer and 343 control subjects in Henan Province. The SNP rs3803662 in TOX3 was genotyped by imLDR technique. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for the SNP between different alleles and breast cancer. RESULTS: There was no statistically significant difference in the distribution of TOX3 rs3803662 allele in different Ki-67 value and HER2 gene status in the case group. The distribution of TOX3 rs3803662 allele between breast cancer and the control group were different. Compared with allele AA and GA, allele GG increased the risk of breast cancer in codominant inheritance (OR=2.19, 95% CI:1.19-4.02) and recessive genetic models (OR=2.06, 95% CI: 1.15-3.70). Further stratifying analysis was conducted based on estrogen receptor status. The SNP rs3803662 showed significant associations with ER status, and was associated with positive ER status in the recessive (OR=1.92; 95% CI:1.00-3.67; P=0.05) and codominant models (OR=2.07; 95% CI:1.05--.08; P=0.036). And this SNP was associated with negative ER status breast cancers in both recessive (OR=2.38; 95% CI:1.10-5.15; P=0.028) and codominant models (OR=2.43; 95% CI:1.08-5.48; P=0.032). But there was no statistically significant difference in each subgroup stratified by ER status. CONCLUSION: This was a verification study in a Han population. In codominant and recessive genetic models, allele GG increased breast cancer risk and was associated with the pathogenesis of different ER status breast cancer. But there was no obvious correlation between this SNP and Ki-67 or HER2 gene. This is the first breast cancer susceptibility loci that is confirmed in Henan population. Our study only analyzes the correlation between the SNP and ER status in breast cancer. More studies and analyses about the association between SNPs and different characteristic of breast cancer should be performed.

Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer.

BACKGROUND & AIMS: The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients. METHODS: Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed. RESULTS: Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%) patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox's regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer. CONCLUSIONS: Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway in triple-negative breast cancer.

This study was conducted to analyze copy number alterations (CNAs) of the genes involved in the G1/S checkpoint signaling pathway of triple-negative breast cancer (TNBC) and to evaluate their clinical value in the prognosis of TNBC. Quantitative multi-gene fluorescence in situ hybridization was used to study CNAs of the genes involved in the G1/S checkpoint signaling pathway, including cyclin d1 (CCND1), c-Myc, p21, cell-cycle-checkpoint kinase 2 gene, p16, retinoblastoma (Rb1), murine double minute 2 (Mdm2) and p53, in 60 TNBC samples and 60 non-TNBC samples. In comparison with the non-TNBC samples, CNAs of the genes involved in the G1/S checkpoint signaling pathway were more frequently observed in the TNBC samples (p = 0.000). Out of a total of eight genes, six (CCND1, c-Myc, p16, Rb1, Mdm2, and p53) exhibited significantly different CNAs between the TNBC group and the non-TNBC group. Univariate survival analysis revealed that the gene amplification of c-Myc (p = 0.008), Mdm2 (p = 0.020) and the gene deletion of p21 (p = 0.004), p16 (p = 0.015), and Rb1 (p = 0.028) were the independent predictive factor of 5-year OS for patients with TNBC. Cox multivariate analysis revealed that the gene amplification of c-Myc (p = 0.026) and the gene deletion of p21 (p = 0.019) and p16 (p = 0.034) were independent prognostic factors affecting the 5-year OS for TNBC. CNAs of the genes involved in the G1/S checkpoint signaling pathway presented a higher rate of incidence in TNBC than in non-TNBC, which could indicate one of the molecular mechanisms for the specific biological characteristics of TNBC. The genes c-Myc, p21, and p16 were correlated with the prognosis of TNBC and therefore may have potential clinical application values in the prognostic prediction of TNBC.

Screening of the miRNAs related to breast cancer and identification of its target genes.

OBJECTIVE: To predict and verify the target genes of the miRNAs related to breast cancer beginning from the miRNA expression profile of human breast cancer. MATERIALS AND METHODS: The total RNA was extracted from cancer tissues and the corresponding paracancerous tissues of eight breast cancer patients, and then miRNAs were separated. Human breast cancer cell line MDA-MB-231 and the normal mammary epithelial cell line HBL-100 were cultured, and the total RNA was extracted, respectively, with separation of miRNAs. The gene chip technology was used to analyze and detect the miRNAs differentially expressed in tissues and cancer cells. The miRNA expression profile of human breast cancer was obtained through chip scanning and data analysis. RESULTS: Through dual-luciferase method, it was verified that PDCD4 and PDCD10 were real target genes of miR-21 and miR-200c, respectively. CONCLUSION: miR-21 and miR-200c are related miRNAs to breast cancer, and they are associated with the occurrence and development of breast cancer.