Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Tarney, Christopher M.; Wang, Guisong; Bateman, Nicholas W.; Conrads, Kelly A.; Zhou, Ming; Hood, Brian L.; Loffredo, Jeremy; Tian, Chunqiao; Darcy, Kathleen M.; Hamilton, Chad A.; Casablanca, Yovanni; Lokshin, Anna; Conrads, Thomas P.; Maxwell, G. Larry

doi:10.1016/j.ajog.2019.06.005

Cited by 14 publications

(9 citation statements)

References 26 publications

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“…By comparing our data with the ones reported by Tarney and colleagues, who conducted a proteomic study on EC serum by using Tandem Mass Tag (TMT) platform, we could confirm that APOA1, APOA4, and CFHR1 were downregulated in the EC serum [ 30 ]. We also performed our Reactome pathway analysis, revealing the dysregulation of several pathways.…”

Section: Discussionsupporting

confidence: 64%

“…The critical aspects of the analytical method employed for the validation could be improved by applying various technologies to biomarker assay development. So far, a few studies on serum endometrial cancer have validated biomarkers with immunochemical methods [ 9 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…We also performed our Reactome pathway analysis, revealing the dysregulation of several pathways. In particular, due to the vital role of the complement cascade in influencing tumor growth and spread [ 30 ], the enrichment of the proteins set in this pathway probably represented a plausible mechanism that considered the progression of the disease. Specifically, CLU was an extracellular chaperone that prevented aggregation of non-native proteins while promoting metastasis in solid tumors and retaining an anti-apoptotic capacity [ 28 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

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Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum

Ura

Biffi

Monasta

et al. 2021

Cancers

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Endometrial cancer is the most common gynecologic malignancy arising from the endometrium. Identification of serum biomarkers could be beneficial for its early diagnosis. We have used 2D-Difference In Gel Electrophoresis (2D-DIGE) coupled with Mass Spectrometry (MS) procedures to investigate the serum proteome of 15 patients with endometrial cancer and 15 non-cancer subjects. We have identified 16 proteins with diagnostic potential, considering only spots with a fold change in %V ≥ 1.5 or ≤0.6 in intensity, which were statistically significant (p < 0.05). Western blotting data analysis confirmed the upregulation of CLU, ITIH4, SERPINC1, and C1RL in endometrial and exosome cancer sera compared to those of control subjects. The application of the logistic regression constructed based on the abundance of these four proteins separated the controls from the cancers with excellent levels of sensitivity and specificity. After a validation phase, our findings support the potential of using the proposed algorithm as a diagnostic tool in the clinical stage.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum

Ura

Biffi

Monasta

et al. 2021

Cancers

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“…Although currently focused on detecting early changes in the epithelial compartment [389,390], our increasing understanding of the complex interactions at play within tissues undergoing malignant transformation presents the opportunity to exploit changes within the surrounding stroma for early detection and patient stratification (Table 2). Changes in immune content and localisation [18], ECM characteristics [391][392][393] and functional gene signatures [145,394,395] all offer potential. Indeed, sequencing approaches have enabled largescale, single-cell resolution characterisation of the immune landscape of over 30 different tumour types [396].…”

Section: Early Detection and Therapeutic Interventionmentioning

confidence: 99%

Microenvironmental modulation of the developing tumour: an immune‐stromal dialogue

2020

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“…Although many protein candidates in blood or vagina samples have been reported as possible biomarkers, most of these studies have only assessed a limited number of candidates or yielded inconsistent results [ 4 , 6 , 7 ]. For instance, several studies found associations of serum level of cancer antigen 15-3 and serum amyloid A with an increased risk of EC, while others showed inverse or null associations [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. These studies using a conventional epidemiological design are potentially subject to selection biases, residual confounding, or reverse causality.…”

Section: Introductionmentioning

confidence: 99%

Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk

Zhu

O’Mara

Liu

et al. 2021

Cancers

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Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (p-values range from 1.14 × 10−10 to 3.04 × 10−4). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.

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Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Cited by 14 publications

References 26 publications

Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum

Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum

Microenvironmental modulation of the developing tumour: an immune‐stromal dialogue

Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk

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