A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification

Mamtani, Manju; Thakre, Tushar P; Kalkonde, Mrunal Y; Amin, Manik; Kalkonde, Yogeshwar; Amin, Amit P.; Kulkarni, Hemant

doi:10.1186/1471-2105-7-442

Cited by 20 publications

(8 citation statements)

References 69 publications

(51 reference statements)

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“…To assess the complementary performance of the potential glycan biomarkers in Table 3, a composite score was derived using multivariate logistic regression [71–73]. First, the abundance of each glycan in each sample was normalized so that low- and high-abundance glycans would be weighted equally.…”

Section: Resultsmentioning

confidence: 99%

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

Hua¹,

Williams²,

Dimapasoc³

et al. 2013

Journal of Chromatography A

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Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n = 46) and healthy control individuals (n = 48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.

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Section: Resultsmentioning

confidence: 99%

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

Hua¹,

Williams²,

Dimapasoc³

et al. 2013

Journal of Chromatography A

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“…From the number of glycopeptide markers found and the AUC values, it can be expected that the glycosite Asn241 present in GP3 is most associated with gastric cancer. To complement and improve the sensitivity and specificity of the markers, we applied a logistic regression model to potential biomarkers and calculated a combined ROC curve [ 57 , 58 , 59 ]. The AUC improved significantly to 0.950 (GP1), 0.929 (GP2), and 0.977 (GP3), respectively ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Detection of Aberrant Glycosylation of Serum Haptoglobin for Gastric Cancer Diagnosis Using a Middle-Up-Down Glycoproteome Platform

Jeong

Kim²,

et al. 2021

JPM

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Gastric cancer is a frequently occurring cancer and is the leading cause of cancer-related deaths. Recent studies have shown that aberrant glycosylation of serum haptoglobin is closely related to gastric cancer and has enormous potential for use in diagnosis. However, there is no platform with high reliability and high reproducibility to comprehensively analyze haptoglobin glycosylation covering microheterogeneity to macroheterogeneity for clinical applications. In this study, we developed a middle-up-down glycoproteome platform for fast and accurate monitoring of haptoglobin glycosylation. This platform utilizes an online purification of LC for sample desalting, and an in silico haptoglobin glycopeptide library constructed by combining peptides and N-glycans to readily identify glycopeptides. In addition, site-specific glycosylation with glycan heterogeneity can be obtained through only a single MS analysis. Haptoglobin glycosylation in clinical samples consisting of healthy controls (n = 47) and gastric cancer patients (n = 43) was extensively investigated using three groups of tryptic glycopeptides: GP1 (including Asn184), GP2 (including Asn207 and Asn211), and GP3 (including Asn241). A total of 23 individual glycopeptides were determined as potential biomarkers (p < 0.00001). In addition, to improve diagnostic efficacy, we derived representative group biomarkers with high AUC values (0.929 to 0.977) through logistic regression analysis for each GP group. It has been found that glycosylation of haptoglobin is highly associated with gastric cancer, especially the glycosite Asn241. Our assay not only allows to quickly and easily obtain information on glycosylation heterogeneity of a target glycoprotein but also makes it an efficient tool for biomarker discovery and clinical diagnosis.

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“…WHR was reported to be a better predictor in a number of countries (14)(15)(16)(17). Also, WC was reported to show superiority over other anthropometric measures in the prediction of type 2 diabetes in British women (18), U.S. men (19), German women (11), and Indian men and women (20). On the other hand, other studies demonstrated that BMI, WHR, WC, and WHtR had similar predictive powers for the risk of type 2 diabetes (24).…”

Section: Discussionmentioning

confidence: 99%

“…Considerable controversy still exists as to which measure most accurately defines body fat distribution. Studies from different countries and ethnicities in the world showed that anthropometric measures have different predictive powers for diabetes and hypertension (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Therefore, the predictive power of anthropometric measures and their appropriate cut-off points should be established for different ethnicities.…”

Section: Introductionmentioning

confidence: 99%

The performance of anthropometric measures to predict diabetes mellitus and hypertension among adults in Jordan

Khader

Batieha

Jaddou

et al. 2019

Preprint

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Objectives This study aimed to evaluate and compare the abilities of waist circumference (WC), body mass index (BMI), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict recently and previously diagnosed diabetes and hypertension and assess their appropriate cut-off values among Jordanian adults.Methods Data from the 2017 cardiovascular risk factors survey were analyzed to achieve the study objective. The survey collected extensive data from a national population-based sample of Jordanian residents. A structured questionnaire was used to collect sociodemographic variables and clinical data. Blood samples were taken for biochemical measurements. Anthropometric characteristics were measured by the same team of trained field researchers.Results This study included a total of 1193 men and 2863 women. Their age ranged from 18 to 90 year with a mean (SD) of 43.8 (14.2) year. WHtR performed better than other anthropometric measures and had a good accuracy (AUC>0.80) among women and fair accuracy among men to predict newly diagnosed diabetes and previously diagnosed diabetes and hypertension. The appropriate cut-off points for anthropometric measures among women were 92 cm form WC, 104 cm for HC, 30 Kg/m 2 for BMI, 0.85 for WHR, and 0.60 for WHtR. For men, the appropriate cut-off points were 100 cm for WC, 104 cm for HC, 27 Kg/m 2 for BMI, 0.93 for WHR, and 0.57 for WHtR.Conclusion WHtR performed better than other anthropometric measures in predicting diabetes and hypertension among adult population in Jordan. We recommend WHtR as a measure of choice with a cut-off value of 0.6 for women and 0.57 for men to predict diabetes and hypertension among Jordanians.

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A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification

Cited by 20 publications

References 69 publications

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

Detection of Aberrant Glycosylation of Serum Haptoglobin for Gastric Cancer Diagnosis Using a Middle-Up-Down Glycoproteome Platform

The performance of anthropometric measures to predict diabetes mellitus and hypertension among adults in Jordan

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