A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

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.

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Raman Spectral Signatures of Serum-Derived Extracellular Vesicle-Enriched Isolates May Support the Diagnosis of CNS Tumors

Cancers ◽

10.3390/cancers13061407 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1407

Author(s):

Matyas Bukva ◽

Gabriella Dobra ◽

Juan Gomez-Perez ◽

Krisztian Koos ◽

Maria Harmati ◽

...

Keyword(s):

Lumbar Disc ◽

Area Under The Curve ◽

Principal Component ◽

Extracellular Vesicle ◽

Classification Performance ◽

Cns Tumors ◽

Clinical Samples ◽

Support Vector ◽

Serum Samples ◽

Raman Spectroscopic

Investigating the molecular composition of small extracellular vesicles (sEVs) for tumor diagnostic purposes is becoming increasingly popular, especially for diseases for which diagnosis is challenging, such as central nervous system (CNS) malignancies. Thorough examination of the molecular content of sEVs by Raman spectroscopy is a promising but hitherto barely explored approach for these tumor types. We attempt to reveal the potential role of serum-derived sEVs in diagnosing CNS tumors through Raman spectroscopic analyses using a relevant number of clinical samples. A total of 138 serum samples were obtained from four patient groups (glioblastoma multiforme, non-small-cell lung cancer brain metastasis, meningioma and lumbar disc herniation as control). After isolation, characterization and Raman spectroscopic assessment of sEVs, the Principal Component Analysis–Support Vector Machine (PCA–SVM) algorithm was performed on the Raman spectra for pairwise classifications. Classification accuracy (CA), sensitivity, specificity and the Area Under the Curve (AUC) value derived from Receiver Operating Characteristic (ROC) analyses were used to evaluate the performance of classification. The groups compared were distinguishable with 82.9–92.5% CA, 80–95% sensitivity and 80–90% specificity. AUC scores in the range of 0.82–0.9 suggest excellent and outstanding classification performance. Our results support that Raman spectroscopic analysis of sEV-enriched isolates from serum is a promising method that could be further developed in order to be applicable in the diagnosis of CNS tumors.

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Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm9072184 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2184 ◽

Cited By ~ 1

Author(s):

Iwona Sidorkiewicz ◽

Magdalena Niemira ◽

Katarzyna Maliszewska ◽

Anna Erol ◽

Agnieszka Bielska ◽

...

Keyword(s):

Pathway Analysis ◽

Mirna Target ◽

Target Genes ◽

Quantitative Polymerase Chain Reaction ◽

Area Under The Curve ◽

Predictive Biomarkers ◽

Predictive Biomarker ◽

Circulating Mirnas ◽

Serum Samples ◽

Roc Curve Analysis

Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

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Raman spectroscopy as a non-invasive diagnostic technique for endometriosis

Scientific Reports ◽

10.1038/s41598-019-56308-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Ugur Parlatan ◽

Medine Tuna Inanc ◽

Bahar Yuksel Ozgor ◽

Engin Oral ◽

Ercan Bastu ◽

...

Keyword(s):

Raman Spectroscopy ◽

Diagnostic Technique ◽

Principal Component ◽

Classification Model ◽

Support Vector ◽

Serum Samples ◽

K Nearest Neighbors ◽

Non Invasive ◽

Unseen Data ◽

Invasive Method

AbstractEndometriosis is a condition in which the endometrium, the layer of tissue that usually covers the inside of the uterus, grows outside the uterus. One of its severe effects is sub-fertility. The exact reason for endometriosis is still unknown and under investigation. Tracking the symptoms is not sufficient for diagnosing the disease. A successful diagnosis can only be made using laparoscopy. During the disease, the amount of some molecules (i.e., proteins, antigens) changes in the blood. Raman spectroscopy provides information about biochemicals without using dyes or external labels. In this study, Raman spectroscopy is used as a non-invasive diagnostic method for endometriosis. The Raman spectra of 94 serum samples acquired from 49 patients and 45 healthy individuals were compared for this study. Principal Component Analysis (PCA), k- Nearest Neighbors (kNN), and Support Vector Machines (SVM) were used in the analysis. According to the results (using 80 measurements for training and 14 measurements for the test set), it was found that kNN-weighted gave the best classification model with sensitivity and specificity values of 80.5% and 89.7%, respectively. Testing the model with unseen data yielded a sensitivity value of 100% and a specificity value of 100%. To the best of our knowledge, this is the first study in which Raman spectroscopy was used in combination with PCA and classification algorithms as a non-invasive method applied on blood sera for the diagnosis of endometriosis.

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Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer

Cancers ◽

10.3390/cancers13092130 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2130

Author(s):

Ruiyang Zou ◽

Sau Yeen Loke ◽

Veronique Kiak-Mien Tan ◽

Swee Tian Quek ◽

Pooja Jagmohan ◽

...

Keyword(s):

Breast Cancer ◽

Area Under The Curve ◽

Circulating Microrna ◽

Breast Lesions ◽

Biomarker Panel ◽

Differentially Expressed Mirnas ◽

Absolute Expression ◽

Benign Breast Lesions ◽

Fold Cross Validation

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively. Absolute expression levels of 324 miRNAs were determined using RT-qPCR. miRNA biomarker panels were identified by: (1) determining differential expression between malignant and benign breast lesions, (2) focusing on top differentially expressed miRNAs, and (3) building panels from an unbiased search among all expressed miRNAs. Two-fold cross-validation incorporating a feature selection algorithm and logistic regression was performed. A six-miRNA biomarker panel identified by the third strategy, had an area under the curve (AUC) of 0.785 and 0.774 in the Discovery and Validation cohorts, respectively, and an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. Biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. Our work demonstrates that circulating miRNA signatures can potentially be used with mammography to differentiate between patients with malignant and benign breast lesions.

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Research on Serum Spectrum Analysis Model Applied to Pathema Identification

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.864-867.486 ◽

2013 ◽

Vol 864-867 ◽

pp. 486-489

Author(s):

Yan Kun Li ◽

Shuo Yang

Keyword(s):

Principal Component ◽

Classification Model ◽

Analysis Model ◽

Recognition Method ◽

Serum Samples ◽

Serum Peptide ◽

Pca Method ◽

Consensus Classification ◽

Peptide Profiles ◽

Practicable Method

The SELDI-TOF MS serum peptide profiles of normal and malignant tumor samples were studied by pattern recognition method. In this study, Partial Least Squares-Discriminate Analysis (PLS-DA) combined with consensus classification model was constructed to predict practical serum samples and compared with the results of principal component analysis (PCA) method. The correctness of consensus PLS-DA classification model for normal and malignant samples was 90% and 84% respectively. So the approach proposed was proved to be a reliable and practicable method for cancer identification.

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Validation of an Enzyme-Linked Immunosorbent Assay for Diagnosis of Human Trichinellosis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00257-08 ◽

2008 ◽

Vol 15 (11) ◽

pp. 1723-1729 ◽

Cited By ~ 63

Author(s):

Maria Angeles Gómez-Morales ◽

Alessandra Ludovisi ◽

Marco Amati ◽

Simona Cherchi ◽

Patrizio Pezzotti ◽

...

Keyword(s):

Immunosorbent Assay ◽

Area Under The Curve ◽

Curve Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Roc Curve Analysis ◽

Epidemiological Surveys ◽

Human Sera ◽

Repeatability And Reproducibility ◽

High Repeatability

ABSTRACT Trichinellosis is a zoonotic disease caused by the consumption of raw or semiraw meat from different animals harboring Trichinella larvae in their muscles. Since there are no pathognomonic signs, diagnosis can be difficult; for this reason, serology is important. The objective of this study was to validate an enzyme-linked immunosorbent assay (ELISA) using excretory/secretory antigens to detect anti-Trichinella immunoglobulin G antibodies in human sera. A total of 3,505 human serum samples were tested. A receiver-operator characteristic (ROC) curve analysis was performed. The accuracy of the test was determined by calculating the area under the curve, which was equal to 0.999, indicating high accuracy. The coefficient of variation calculated for data from four serum samples in eight working sessions was no higher than 5% for the positive sera or 14% for the negative sera. Moreover, the analysis of the differences in optical density between duplicates indicated a high repeatability for the ELISA. At the ROC optimized cutoff, the sensitivity and specificity of the test were, respectively, 99.2% and 90.6% (specificity of 95.6% when excluding the samples from multiparasitized persons from Tanzania). The validated ELISA showed good performance in terms of sensitivity, repeatability, and reproducibility, whereas the specificity was limited. These results suggest that this test is suitable for detecting anti-Trichinella antibodies in human sera for diagnostic purposes, whereas its use in epidemiological surveys could be questionable.

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A Comparative Assessment of MR BI-RADS 4 Breast Lesions With Kaiser Score and Apparent Diffusion Coefficient Value

Frontiers in Oncology ◽

10.3389/fonc.2021.779642 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lingsong Meng ◽

Xin Zhao ◽

Lin Lu ◽

Qingna Xing ◽

Kaiyu Wang ◽

...

Keyword(s):

Diffusion Coefficient ◽

Apparent Diffusion Coefficient ◽

Breast Imaging ◽

Diagnostic Performance ◽

Area Under The Curve ◽

Lower Sensitivity ◽

Breast Lesions ◽

Roc Curve Analysis ◽

Apparent Diffusion Coefficient Value ◽

Apparent Diffusion

ObjectivesTo investigate the diagnostic performance of the Kaiser score and apparent diffusion coefficient (ADC) to differentiate Breast Imaging Reporting and Data System (BI-RADS) Category 4 lesions at dynamic contrast-enhanced (DCE) MRI.MethodsThis was a single-institution retrospective study of patients who underwent breast MRI from March 2020 to June 2021. All image data were acquired with a 3-T MRI system. Kaiser score of each lesion was assigned by an experienced breast radiologist. Kaiser score+ was determined by combining ADC and Kaiser score. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of Kaiser score+, Kaiser score, and ADC. The area under the curve (AUC) values were calculated and compared by using the Delong test. The differences in sensitivity and specificity between different indicators were determined by the McNemar test.ResultsThe study involved 243 women (mean age, 43.1 years; age range, 18–67 years) with 268 MR BI-RADS 4 lesions. Overall diagnostic performance for Kaiser score (AUC, 0.902) was significantly higher than for ADC (AUC, 0.81; p = 0.004). There were no significant differences in AUCs between Kaiser score and Kaiser score+ (p = 0.134). The Kaiser score was superior to ADC in avoiding unnecessary biopsies (p < 0.001). Compared with the Kaiser score alone, the specificity of Kaiser score+ increased by 7.82%, however, at the price of a lower sensitivity.ConclusionFor MR BI-RADS category 4 breast lesions, the Kaiser score was superior to ADC mapping regarding the potential to avoid unnecessary biopsies. However, the combination of both indicators did not significantly contribute to breast cancer diagnosis of this subgroup.

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201Tl Scintigraphy in the Evaluation of Palpable and Nonpalpable Breast Lesions: Correlation with Mammography and Ultrasonography

Nuklearmedizin ◽

10.1055/s-0038-1629848 ◽

1997 ◽

Vol 36 (08) ◽

pp. 282-288 ◽

Cited By ~ 8

Author(s):

T. Atasever ◽

A. Özdemir ◽

I. Öznur ◽

N. I. Karabacak ◽

N. Gökçora ◽

...

Keyword(s):

Final Diagnosis ◽

Lower Sensitivity ◽

Breast Lesions ◽

Breast Cancers ◽

Combined Use ◽

Malignant Breast ◽

Malignant Lesions ◽

Benign Breast Lesions ◽

Palpable Breast ◽

Metastatic Sites

Summary Aim: Our goal was to determine the clinical usefulness of TI-201 to identify breast cancer in patients with suspicious breast lesions on clinical examination, and/or abnormal radiologic (mammography and/or ultrasonography) findings. Methods: TI-201 scintigraphy were performed in sixty-eight patients with 70 breast abnormalities (51 palpable, 19 nonpalpable) and compared with mammography and ultrasonography (US). Early (15 min) and late (3 h) images of the breasts were obtained following the injection of 111 MBq (3 mCi) of TI-201. Visual and semiquantitative interpretation was performed. Results: Final diagnosis confirmed 52 malignant breast lesions and 18 benign conditions. TI-201 visualized 47 of 52 (90%) overall malignant lesions. Thirty-eight of 40 (95%) palpable and 9 of 12 (75%) nonpalpable breast cancers were detected by TI-201 scintigraphy. The smallest mass lesion detected by TI-201 measured 1.5x1.0 cm. Eleven breast lesions were interpreted as indeterminate by mammography and/or sonography. TI-201 scintigraphy excluded malignancy in 7 of 8 (88%) patients with benign breast lesions interpreted as indeterminate. Five of the 18 (28%) benign breast lesions showed TI-201 uptake. None of the fibroadenoma and fibrocystic changes accumulated TI-201. TI-201 scintigraphy, mammography and ultrasonography showed 90%, 92%, 85% overall sensitivity and 72%, 56%, 61% overall specificity respectively. Twenty-one of the 28 (75%) axillary nodal metastatic sites were also detected by TI-201. In malignant and benign lesions, early and late lesion/contralateral normal side (L/N) ratios were 1.58 ± 0.38 (mean ± SD) and 1.48 ± 0.32 (p >0.05), 1.87 ± 0.65 and 1.34 ± 0.20 (p<0.05) respectively. The mean early and late L/N ratios of malignant and benign groups did not show statistical difference (p>0.05). Conclusion: Overall, TI-201 scintigraphy was the most specific of the three methods and yielded favourable results in palpable breast cancers, while it showed lower sensitivity in nonpalpable cancers and axillary metastases. Combined use of TI-201 scintigraphy with mammography and US seems to be useful in difficult cases, such as dense breasts and indeterminate breast lesions.

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TO DETERMINE THE ROLE OF CA125 IN THE DIAGNOSIS OF ACUTE APPENDICITIS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i7.1276 ◽

2020 ◽

Vol 4 (7) ◽

Author(s):

Vinod Kumar ◽

Bhupen Songra ◽

Richa Jain ◽

Deeksha Mehta

Keyword(s):

Acute Appendicitis ◽

Clinical Diagnosis ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Ca 125 ◽

Care Hospital ◽

Serum Samples ◽

Roc Curve Analysis ◽

Surgery Department

Background: the present study was under taken to determine the role of CA-125 in the diagnosis of acute appendicitis (AA), to prevent its complications and also in preventing negative appendicectomies in tertiary care hospital. Methods: The study was conducted at a tertiary care and research center between 01/03/2018 to 30/06/2019. Patients admitted to the surgery department with diagnosis of AA were considered for the study. After informed consent, a, standardized history was obtained as a case Performa. Serum samples from all the cases with clinical diagnosis of AA were obtained and stored. Only the cases with histopathologically approved AA were included in the study. Cases operated for clinical diagnosis of AA, but not histopathologically proven AA was not included in the study. CA125 levels in cases with definitive diagnosis of AA were measured. Results: In present study, ROC curve analysis revealed the sensitivity of 87.27 % and specificity of 90.91 % when the CA 125 cut-off value of > 16.8 was taken to diagnose acute appendicitis. AUC was 0.911 with a standard error of 0.0292. Conclusion: In this study we have observed that CA125 showed a positive correlation with acute appendicitis, that was statistically not significant (P>0.05). We didn’t evaluate the correlation with the disease severity. We consider that CA125 can be used as a marker in acute appendicitis cases although further research is still needed. Keywords: CA125, Acute Appendicitis, Surgery.

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Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽

10.3390/biom10071083 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1083

Author(s):

Aleksandra Filimoniuk ◽

Agnieszka Blachnio-Zabielska ◽

Monika Imierska ◽

Dariusz Marek Lebensztejn ◽

Urszula Daniluk

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

High Performance ◽

Area Under The Curve ◽

Study Groups ◽

Diagnostic Value ◽

Serum Samples ◽

Specificity And Sensitivity ◽

Potential Biomarker ◽

Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

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