Global characteristics and trends in research on Candida auris.

Introduction: Candida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients' skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results. Method: A bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva's articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for 'drug resistance,' 'antifungal susceptibility test,' 'infection,' 'Candida auris,' and 'identification.' The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris. Conclusion: The bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris.

Phenotypic and genetic features of a novel clinically isolated rough morphotype Candida auris.

Introduction: Candida auris is a newly emerging pathogenic fungus of global concern and has been defined by the World Health Organization (WHO) as a member of the critical group of the most health-threatening fungi. Methods: This study reveals and reports for the first time that a rough morphotype C. auris strain causes urinary tract infections in non-intensive care unit (ICU) inpatients. Furthermore, the morphology, the scanning electronmicroscopy (SEM), Whole-genome resequencing and RNA sequencing of C. auris possessing rough morphotype colonies compared to their smooth morphotype counterparts. Results: The newly identified phenotypic variation of C. auris appears round, convex, dry, and burr-like with a rough texture. SEM shows that rough type C. auris has a rough and uneven colony surface with radial wrinkles and irregular spore arrangement. Cells of the rough morphotype C. auris naturally aggregate into clusters with tight connections in the liquid, and it seems that the cell division is incomplete. A genome-wide analysis of the rough type C. auris confirmed its genetic association with the smooth type of C. auris prevalent in China (Shenyang) two years ago; however, single nucleotide polymorphism (SNP) mutations of five genes (ACE2, IFF6, RER2, UTP20, and CaO19.5847) were identified more recently. RNA-seq revealed IFF2/HYR3, DAL5, PSA31, and SIT1 were notably up-regulated, while multiple cell wall-associated genes (ALS1, MNN1, PUL1, DSE1, SCW11, PGA38, RBE1, FGR41, BGLI, GIT3, CEP3, and SAP2) were consistently down-regulated in rough morphotype C. auris. Discussion: The rough phenotypic variation of C. auris is likely to be related to the structural and functional changes in cell wall proteins. This novel rough morphotype C. auris will provide a basis for further studies concerning the evolutionary characteristics of C. auris.

High-efficient disturbance event recognition method of ϕ-OTDR utilizing region-segmentation differential phase signals.

We demonstrate a disturbance event recognition method based on region segmentation, which utilizes differential phase signals of a phase-sensitive optical time-domain reflectometer (ϕ-OTDR) to recognize disturbance events efficiently. The long-haul sensing fiber is divided into subsensing regions; whereas the phase signals at the two end points of the subsensing regions are subtracted, unwrapped, and differenced to represent the disturbance information. Feature extraction and classification are performed separately on the subsensing regions datasets. The experimental results indicate that the average recognition accuracy of the region-segmentation-based event recognition method is up to 92.9%. Compared to the method without region segmentation, this proposed method improves the average recognition accuracy by 8%; whereas the recognition time of three disturbance events on a 14.8-km sensing system is only 0.39 s. The proposed method provides significant support for the development of disturbance event recognition of the ϕ-OTDR sensor system.

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study.

BACKGROUND: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. OBJECTIVE: To define the characteristics of phenotypic and genetic HoFH probands from mainland China. METHODS: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. RESULTS: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. CONCLUSIONS: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.

Remnant Lipoprotein Cholesterol as a Factor Related to Adult Fatty Liver Disease.

CONTEXT: Dyslipidemia is related to fatty liver disease (FLD), whose relationship with remnant lipoprotein cholesterol (RLP-C), a component of blood lipids, remains unclear. OBJECTIVE: To clarify the correlation between RLP-C and the occurrence and severity of FLD and establish an FLD discriminant model based on health check indicators. METHODS: Retrospective study of participants who underwent health check-up in the First Affiliated Hospital of China Medical University (Shenyang, China) between January and December 2019. We categorized participants according to liver ultrasound results and analyzed the correlation between RLP-C and occurrence of FLD (n = 38 885) through logistic regression, restricted cubic spline, and receiver operating characteristic curve. We categorized the severity of FLD according to the control attenuation parameter and analyzed the correlation between RLP-C and FLD severity through multiple logistic regression; only males were included (n = 564). RESULTS: The adjusted OR (aOR) per SD between RLP-C and FLD was 2.33 (95% CI 2.21-2.46, P < .001), indicating a dose-response relationship (P < .0001). The optimal cut-off value of RLP-C was 0.45 mmol/L and the area under the curve (AUC) was 0.79. The AUC of the 8-variable model was 0.89 in both the training and the validation sets. FLD severity was related to the level of RLP-C (aOR per SD = 1.29, 95% CI 1.07-1.55, P = .008). CONCLUSION: RLP-C has a strong positive correlation with FLD occurrence and FLD severity. These results may help clinicians identify and implement interventions in individuals with high FLD risk and reduce FLD prevalence.

Genomic epidemiology of Candida auris in a general hospital in Shenyang, China: a three-year surveillance study.

Candida auris is an emerging pathogenic fungal species found worldwide. Since April 2016, C. auris colonization/infection cases have been found in a general hospital in Shenyang, China. The genome-based phylogenetic studies of these isolates remain undefined. In the current study, the microbiological characteristics and antifungal susceptibility of these C. auris isolates, which were collected in Shenyang during the three-year period (2016-2018), were investigated. Whole-genome sequencing was applied to investigate the genetic variation and molecular epidemiological characteristics. A total of 93 C. auris isolates, including 92 clinical isolates and 1 environmental screening isolate were identified. Among the investigated wards, the C. auris cases were the most prevalent (97.4%, 37/38) in four intensive care units (ICUs). The Shenyang isolates carrying the VF125AL mutation in the key drug-resistance gene ERG11 were mainly fluconazole resistant and formed a distinct subclade under the South African clade according to the phylogenetic and population structural analyses. In addition, the Shenyang subclade was found to be closely related to the British subclade in the aspect of genetic distance. As a conclusion, this study provides an important clue for revealing the origin of C. auris found in Shenyang and could also contribute to improve the understanding of the epidemiological characteristics of C. auris worldwide.

Integrated analysis of microRNA and mRNA expression profiles in homozygous familial hypercholesterolemia patients and validation of atherosclerosis associated critical regulatory network.

Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA-mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.

Clinical Characteristics and Outcomes of Candidemia Caused by Meyerozyma guilliermondii Complex in Cancer Patients Undergoing Surgery.

Although Meyerozyma guilliermondii complex is an uncommon cause of invasive candidiasis worldwide, reported cases, mainly regarding bloodstream infections, increased over years, and patients with cancer who have undergone recent surgery are most commonly affected. However, the clinical characteristics and outcomes of candidemia caused by M. guilliermondii complex remain poorly understood. A retrospective case-control study was conducted to evaluate the clinical characteristics and mortality of candidemia caused by M. guilliermondii complex in cancer patients undergoing surgery. Demographic and clinical data were collected from the hospital medical records system with a standardized data collection form and were analyzed with SPSS 20.0. Sixty-six cancer patients who have undergone recent surgery and were diagnosed with candidemia caused by M. guilliermondii complex were included in the study. Regarding the clinical manifestations, most patients' body temperatures ranged from 38 to 40 °C, with a median fever duration of 4 (IQR: 3-6) days. Multivariate analysis indicated that the presence of central venous catheter (OR: 6.68; 95% CI 2.80-15.94) and gastric tube (OR: 3.55; 95% CI 1.22-10.34) were independent risk factors for M. guilliermondii complex fungemia. The 30-day crude mortality of candidemia caused by M. guilliermondii complex was 12.1%, twice that of the control group. Moreover, increased WBC count, age ≥ 60 years, septic shock, and ICU admission were identified as predictors of mortality through univariate analysis. These findings will provide a foundation for the clinical management of candidemia caused by M. guilliermondii complex in post-surgical cancer patients.

Pan-cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential.

As the most critical alternative splicing regulator, heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be implicated in various aspects of cancer. However, the comprehensive understanding of hnRNPs in cancer is still lacking. The molecular alterations and clinical relevance of hnRNP genes were systematically analysed in 33 cancer types based on next-generation sequence data. The expression, mutation, copy number variation, functional pathways, immune cell correlations and prognostic value of hnRNPs were investigated across different cancer types. HNRNPA1 and HNRNPAB were highly expressed in most tumours. HNRNPM, HNRNPUL1, and HNRNPL showed high mutation frequencies, and most hnRNP genes were frequently mutated in uterine corpus endometrial carcinoma (UCEC). HNRNPA2B1 showed widespread copy number amplification across various cancer types. HNRNPs participated in cancer-related pathways including protein secretion, mitotic spindle, G2/M checkpoint, DNA repair, IL6/JAK/STAT3 signal and coagulation, of which hnRNP genes of HNRNPF, HNRNPH2, HNRNPU and HNRNPUL1 are more likely to be implicated. Significant correlation of hnRNP genes with T help cells, NK cells, CD8 positive T cells and neutrophils was identified. Most hnRNPs were associated with worse survival of adrenocortical carcinoma (ACC), liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD), whereas hnRNPs predicted better prognosis in kidney renal clear cell carcinoma (KIRC) and thymoma (THYM). The prognosis analysis of KIRC suggested that hnRNPs gene cluster was significantly associated with overall survival (HR = 0.5, 95% CI = 0.35-0.73, P = 0.003). These findings provide novel evidence for further investigation of hnRNPs in the development and therapy of cancer in the future.

A study on reference interval transference via linear regression.

Background Reference intervals (RIs) transference can expand the applicability of established RIs. However, the study on transference methodology is insufficient, and RIs validation based on small samples cannot adequately identify transferred risk under complex situations. This study aimed to find appropriate conditions to ensure the effect of transference. Methods We established the RIs of Roche and Beckman systems for 27 analytes based on 681 healthy individuals. Roche RIs were converted into the Beckman RIs using linear regression (least squares method) which is divided into two methods - Methodref (500 test numbers with relatively narrow data range) and Methodep (80 test numbers with relatively wide data range). Taking the RIs established by Beckman results as standard, we assessed the accuracy, precision and trueness of transferred results under various conditions. Results A total of 29.6% and 48.1% of analytes were consistent between the two systems for the lower and upper reference limits, respectively. The concordance rates between transferred and measured RIs for Methodref were up to 74.1% and 92.6%, which were better than Methodep (44.4% and 59.3%). The CV of transferred reference limits decreased gradually with increasing test number under the same data range. For most analytes, excluding some electrolyte tests, we could obtain accurate results when r > 0.800 and the test number was sufficient regardless of the regression equation types. Conclusions Transferability of RIs is affected by many factors, such as correlation, test number, regression equation type, and quality requirement. To reduce the risk of transference, it is very important to select right method with reasonable conditions.

Independent Severe Cases of Heterozygous Familial Hypercholesterolemia Caused by the W483X and Novel W483G Mutations in the Low-Density Lipoprotein Receptor Gene That Were Clinically Diagnosed as Homozygous Cases.

Background and Aims: The genetic spectrum underlying familial hypercholesterolemia (FH) remains unclear, especially in northeastern China. The aim of this study was to delineate the FH genetic spectrum and identify specific characteristics of FH patients in this region. Materials and Methods: The family history, personal medical history, and lifestyle habits of two unrelated patients clinically diagnosed with homozygous FH were recorded. DNA samples of the patients and their relatives were subjected to a newly designed next-generation sequencing panel using an Illumina Miseq platform. Detected variants were annotated and functionally predicted with in silico algorithms, and protein structures were modeled. Results: The patients' cholesterol levels were effectively reduced to 33.8% and 17.2% of the original level under conventional ezetimibe and statin treatment. Two pathogenic mutations, W483X and the novel mutation W483G, in the low-density lipoprotein receptor (LDLR) gene were identified. Both patients were heterozygous for the respective mutations. Under a high cholesterol/carbohydrate diet, these mutations could trigger a severe FH phenotype, but both patients responded well to regular medical treatments and dietary control. The W483X mutation results in a premature stop codon, leading to incomplete protein formation. Although the W483G mutation results in translation of the complete protein with no apparent structural difference, it still led to a severe FH phenotype similar to W483X. Conclusions: Identification of the novel W483G mutation expands the genetic spectrum of FH. Both mutations cause a severe FH phenotype under certain conditions, suggesting that W483 is important for LDLR function, highlighting potential targets for genetic screening or drug development.

Association of VAMP8 rs1010 Polymorphism with Host Susceptibility to Pulmonary Tuberculosis in a Chinese Han Population.

Aims: Autophagic eradication of pathogenic microbes, including Mycobacterium tuberculosis (Mtb), is an effective host immune process that protects hosts from developing diseases associated with intracellular pathogens. This study was designed to investigate the association between the single nucleotide polymorphisms (SNPs) of the autophagy-related genes VAMP8 and VTI1B, and the susceptibility to pulmonary tuberculosis (PTB) in a Chinese Han population. Materials and Methods: Two SNPs, rs1010 from the VAMP8 gene and rs15493 from the VTI1B gene, were examined in 202 PTB patients and 216 healthy controls using high-resolution melt-polymerase chain reaction. Results: The rs1010 SNP genotypes AG (p = 0.028) and GG (p = 0.016) were associated with increased susceptibility to PTB. However, the VTI1B rs15493 SNP had no impact on the susceptibility to PTB (p > 0.05). Conclusions: Our study demonstrated that the rs1010 SNP of VAMP8 gene was significantly associated with the susceptibility to PTB. This result suggests that rs1010 genotyping could be used as prognostic biomarker to predict the risk of Mtb infection and/or PTB disease development after Mtb infection in the Chinese Han population.

First cases and risk factors of super yeast Candida auris infection or colonization from Shenyang, China.

For the first time, we identified 15 cases of Candida auris in Shenyang, China, and then performed a risk factor assessment for these patients compared with 30 control subjects who were hospitalized in the same ward during the same period of time as the infected patients. We found that diarrhea, gastrointestinal decompression, infection, or colonization with other Candida isolates (especially Candida albicans) and tetracycline antibiotics were all risk factors for C. auris infection or colonization. Diarrhea and tetracycline antibiotics were independent risk factors. We suggest clinicians pay special attention to the emergence of multidrug-resistant C. auris infections or colonization.

Vitamin D aggravates breast cancer by inducing immunosuppression in the tumor bearing mouse.

The aim of this approach is to test the effects and related mechanism of vitamin D (VD) treatment on the outcomes of breast cancer. BALB/c mice were injected with 4T1 breast cancer cell suspension. The test group was treated with VD reagent. The survival and tumor size of mice were observed. The proliferation of 4T1 in vitro was detected by MTS analysis. The changes of immune parameters and microenvironment in mice were evaluated by flow cytometry and real-time RT-PCR. Our results demonstrate that VD administration caused a decline in survival time and raising the volume of tumor, the decreasing numbers of CD3+CD4+ T, CD3+CD8+ T and CD4+T-bet+IFN-γ+ Th1 cells and transcriptions of T-bet and IFN-γ, an increasing number of myeloid-derived suppressor cells and transcription of TGF-ß. Our data suggest that the routine clinical application of any strategies targeting VD status for breast cancer therapy is deserved serious consideration.

Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells.

The aim of the present study was to assess the effects of sprouty homolog 2 (SPRY2) gene regulation by miR-21 on the occurrence, development and tumor metastasis in multiple myeloma (MM). The miR-21 expression lentiviral vector (LV)-anti-miR-21 and a liposome transfection method were used to screen MM cell lines with stable silent SPRY2. Real-time quantitative polymerase chain reaction (PCR) and western blot analyses were used to detect SPRY2 expression and miR-21 protein expression levels. An MTT assay was used to assess cell proliferation. Flow cytometry was used for analysis of cell cycle. A scratch test/wound healing assay was used to detect the cell migration ability. A Transwell assay was used to detect the cell invasion ability. Real-time quantitative PCR and western blot analysis showed that in the MM cell lines with high endogenous miR-21 expression (RPMI8226 and KM3), SPRY2 expression was significantly lower. Conversely, in the U266 cell line with low endogenous miR-21 expression, SPRY2 expression was significantly higher, and the gray values of miR-21 and SPRY2 protein in the respective cell lines showed statistically significant differences (P<0.01). Following transfection of U266 cells, the expression of miR-21 in the U266/LV-anti-miR21 lentiviral multiplicity of infection (MOI) 20 group and -MOI 40 group decreased significantly compared with that in the untransfected U266 group (P<0.05). SPRY2 protein expression in U266 cells transfected with miR-21 mimics was significantly reduced compared with that in the non-transfected (untreated) group and the negative control-transfected group (P<0.01). An MTT assay showed that compared with the non-transfected and negative control groups, the cell growth rate as well as the proliferation rate were significantly decreased in the transfection group 48, 72 and 96 h after transfection (P<0.01). Flow cytometric analysis showed that 48 and 72 h after transfection of U266 cells with miR-21 mimics, the apoptotic rates were (24.7 ± 1.97 and 38.6 ± 1.56%) in the U266 group, (27.3 ± 1.72 and 37.3 ± 1.59%) in the siRNA group and (12.7 ± 1.27 and 22.1 ± 1.63%) in the U266/miR-21 group. Compared with the two control groups, the apoptotic rate in the U266/miR-21 group was significantly decreased and the G0/G1 phase cell population was significantly reduced (P<0.05). Scratch experiments showed that the cell migration ability was significantly reduced in the transfection group 24 and 48 h after transfection (P<0.05). A Transwell invasion assay confirmed that the number of U266 cells which migrated through a Matrigel-covered polyphosphate membrane significantly decreased in the transfection group 24 and 48 h after transfection. The cell-penetrating ability was also significantly decreased (P<0.05). In conclusion, the downregulation of SPRY2 gene expression mediated by miR-21 promotes the proliferation and invasion of MM cells in vitro, suggesting that miR-21 may be a novel potential molecular therapeutic target in the treatment of MM.

Correlation between microRNA­21 and sprouty homolog 2 gene expression in multiple myeloma.

The aim of the present study was to investigate the expression level of microRNA 21 (miR­21) in the peripheral blood of patients with multiple myeloma (MM) and to investigate the correlation between miR­21 and sprouty homolog 2 (SPRY2) gene expression levels in MM. A total of 30 patients with MM, 15 with monoclonal gammopathy of undetermined significance (MGUS) and 20 normal control (NC) outpatients were selected for the detection of miR­21 and SPRY2 expression using reverse transcription-quantitative polymerase chain reaction. In addition, western blot analysis was performed to detect the expression of miR­21 and SPRY2 in MM cell lines. The expression of miR­21 in U­266 cells following lipofectamine transfection of fluorescence­labeled miR­21 mimic/inhibitor was observed using a fluorescence microscope and the expression level of SPRY2 in the miR­21 mimic/inhibitor­transfected U­266 cells was detected using western blot analysis. The miR­21 expression level in the circulating serum of the MM patient group was significantly higher (P<0.01) than that of the MGUS and NC groups. The MM cell lines with high endogenous miR­21 expression exhibited an expression level of SPRY2 that was significantly lower than that in the MM cells with low endogenous miR­21 expression. The transfection efficiency of fluorescence­labeled miR­21 mimic/inhibitor was >90%. Compared with the miR­21 expression level in untreated U­266 cells (0.82±0.13), the expression level of miR­21 was increased by 120.2­fold in miR­21 mimic­transfected cells (98.6±14.2; P<0.001) and was decreased by 61.9% in the miR­21 inhibitor­transfected cells (0.37±0.06; P<0.05). The grayscale value of protein bands demonstrated that SPRY2 protein expression significantly decreased in miR­21 mimic­transfected U­266 cells compared with that in the inhibitor­transfected, siRNA­transfected and untreated cells (P<0.01). miR­21 may represent a negative regulator involved in the downregulation of SPRY2 in MM. miR­21 is closely associated with the pathogenesis, progression and prognosis of MM and may thus be used as an indicator of poor MM prognosis.

Aberrant promoter methylation of HIN-1 gene may contribute to the pathogenesis of breast cancer: a meta-analysis.

We conducted the present meta-analysis of relevant cohort studies to evaluate whether promoter methylation of the high in normal-1 (HIN-1) gene contributes to breast cancer. The MEDLINE (1966 ~ 2013), Cochrane Library (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and Chinese Biomedical (CBM) (1982 ~ 2013) databases were searched without any language restrictions. Meta-analyses were conducted using Stata software (version 12.0; Stata Corporation, College Station, TX, USA). Crude odds ratios (ORs) with their 95 % confidence interval (CI) were calculated. Nine clinical cohort studies that enrolled a total of 693 breast cancer patients were included in the meta-analysis. The results of our meta-analysis demonstrated that HIN-1 methylation frequency in cancer tissue was significantly higher than that of normal and benign tissues (cancer tissue vs. normal tissue: OR = 52.60, 95 % CI = 33.77 ~ 81.92, P < 0.001; cancer tissue vs. benign tissue: OR = 2.38, 95 % CI = 1.53 ~ 3.70, P < 0.001; respectively). Ethnicity-stratified analysis indicated that HIN-1 promoter methylation was correlated with the pathogenesis of breast cancer among both Asians and Caucasians (all P < 0.05). Our findings provide empirical evidence that aberrant HIN-1 promoter methylation may contribute to the pathogenesis of breast cancer. Thus, aberrant HIN-1 promoter methylation could be an independent and important biomarker used in predicting the prognosis and progression of breast cancer.