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1.
Cancers (Basel) ; 11(12)2019 Nov 26.
Article in English | MEDLINE | ID: mdl-31769433

ABSTRACT

Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

2.
Oncotarget ; 9(16): 12796-12804, 2018 Feb 27.
Article in English | MEDLINE | ID: mdl-29560110

ABSTRACT

Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model.

3.
J Clin Pathol ; 67(12): 1032-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25217710

ABSTRACT

AIM: We aimed to assess the one step nucleic acid amplification (OSNA) assay as an intraoperative method in comparison with frozen sections (FS) for detection of metastasis in sentinel lymph nodes (SLNs) of breast cancer. METHOD: 100 SLNs from patients with breast carcinoma were enrolled within a 3-month period. Alternate 2 mm node slices were subjected to routine FS, and later to permanent histology, and the rest for automated molecular detection of CK19 mRNA using OSNA. FS and OSNA findings were compared with permanent histology results. Difference in turnaround time was also noted. RESULTS: With permanent histology as gold standard, OSNA was discrepant in 8 of 98 (3 false negative, 5 false positive) included SLNs whereas FS had 2 false negative cases. FS had higher sensitivity (89%, p=<0.001), specificity (100%, p=0.001) and concordance rate (98%) than OSNA (83%, 94% and 92%, respectively). FS showed almost perfect agreement (κ=0.929) whereas OSNA showed substantial agreement (κ=0.740) when compared with permanent histology. OSNA turnaround time was twice longer (mean of 47.7 min) than FS. CONCLUSIONS: Automation of SLN assessment using OSNA is a potentially useful intraoperative diagnostic tool with acceptable accuracy. Discordant findings in this study may be due to sampling allocation. Since OSNA is more time-consuming, its practical advantage over routine FS requires further study in view of current technical workflow considerations.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , Lymphatic Metastasis/diagnosis , Nucleic Acid Amplification Techniques/methods , Sentinel Lymph Node Biopsy , Female , Humans , Intraoperative Period , Keratin-19/analysis , Sensitivity and Specificity , Time Factors
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