{
    "assessed_biomarker_entity": "WAP four-disulfide core domain protein 2 (WFDC2)",
    "assessed_entity_type": "protein",
    "components": {
        "protein": [
            {
                "accession": "Q14508-1",
                "name": "WAP four-disulfide core domain protein 2",
                "evidence": [
                    {
                        "id": "GLY_000625",
                        "database": "GlyGen",
                        "url": "https://data.glygen.org/GLY_000625"
                    },
                    {
                        "id": "21633297",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/21633297"
                    },
                    {
                        "id": "19732003",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/19732003"
                    },
                    {
                        "id": "32347972",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/32347972"
                    },
                    {
                        "id": "27446579",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/27446579"
                    },
                    {
                        "id": "32347972",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/32347972"
                    },
                    {
                        "id": "32347972",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/32347972"
                    },
                    {
                        "id": "32347972",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/32347972"
                    },
                    {
                        "id": "32347972",
                        "database": "PubMed",
                        "url": "https://glygen.org/publication/PubMed/32347972"
                    }
                ]
            }
        ],
        "glycan": []
    },
    "instances": [
        {
            "best_biomarker_type": "prognostic",
            "status": "increased WFDC2 level",
            "notes": "Measured in serum (UN:0001977) as well|Synonym: Human epididymis protein 4",
            "literature_evidence": "Early diagnosis is the most important determinant of early survival for ovarian cancer, and increased levels of HE4, in combination with CA125, is used as a diagnostic marker for ovarian cancer. HE4 levels were found to be significantly higher in individuals with ovarian cancer. Combining both HE4 and CA125 yielded specificity for ovarian cancer of 100%. [PMID:21633297] Preliminary data show that HE4 may have more potential than cancer antigen 125 in discriminating benign from cancerous ovarian masses, and has the strongest correlation with endometrial cancer of all markers tested to date. Utilizing risk stratification, a panel of biomarkers including HE4 may ultimately be useful for detecting ovarian and endometrial cancer at an early stage in patients at high risk. [PMID:19732003] This is the first report with such a substantial evaluation of cancer biomarkers on a large patient population of COVID-19. Our data demonstrate that levels of serum HE4, CYFRA21-1, CEA, CA125, CA153, SCC, and NSE are positively associated with CRP, a crucial factor in correlation with the severity of the disease. We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19. [PMID:32347972]",
            "loinc_code": "55180-4",
            "tissue": {
                "name": "blood",
                "namespace": "UBERON",
                "id": "0000178",
                "url": "http://purl.obolibrary.org/obo/UBERON_0000178"
            },
            "disease": {
                "disease_id": "DOID:2394",
                "recommended_name": {
                    "id": "DOID:2394",
                    "resource": "Disease Ontology",
                    "url": "http://disease-ontology.org/term/DOID:2394",
                    "name": "ovarian cancer",
                    "description": "A female reproductive organ cancer that is located_in the ovary."
                },
                "synonyms": [
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "malignant Ovarian tumor",
                        "description": ""
                    },
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "malignant tumour of ovary",
                        "description": ""
                    },
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "ovarian neoplasm",
                        "description": ""
                    },
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "ovary neoplasm",
                        "description": ""
                    },
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "primary ovarian cancer",
                        "description": ""
                    },
                    {
                        "id": "DOID:2394",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:2394",
                        "name": "tumor of the Ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0011931",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0011931",
                        "name": "ovarian cancer, susceptibility to, 1",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0011931",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0011931",
                        "name": "OVCAS1",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0011931",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0011931",
                        "name": "ovarian cancer, susceptibility to",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0011931",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0011931",
                        "name": "ovarian cancer, susceptibility to, 1",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian cancer",
                        "description": "A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas."
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian neoplasm",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovary neoplasm",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "tumor of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "tumour of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "cancer of ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "cancer of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant neoplasm of ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant neoplasm of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant ovarian neoplasm",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant ovarian tumor",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant ovarian tumour",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant ovary neoplasm",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant tumor of ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant tumor of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant tumour of ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "malignant tumour of the ovary",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian cancer",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian cancer, somatic",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian malignant tumor",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian malignant tumour",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovary cancer",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "ovarian cancer, epithelial",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0008170",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0008170",
                        "name": "primary ovarian cancer",
                        "description": ""
                    },
                    {
                        "id": "MIM:167000",
                        "resource": "MIM",
                        "url": "https://www.omim.org/entry/167000",
                        "name": "Ovarian cancer",
                        "description": "Ovarian cancer"
                    }
                ]
            },
            "evidence": [
                {
                    "id": "GLY_000625",
                    "database": "GlyGen",
                    "url": "https://data.glygen.org/GLY_000625"
                },
                {
                    "id": "21633297",
                    "database": "PubMed",
                    "url": "https://glygen.org/publication/PubMed/21633297"
                },
                {
                    "id": "19732003",
                    "database": "PubMed",
                    "url": "https://glygen.org/publication/PubMed/19732003"
                },
                {
                    "id": "32347972",
                    "database": "PubMed",
                    "url": "https://glygen.org/publication/PubMed/32347972"
                }
            ]
        },
        {
            "best_biomarker_type": "diagnostic",
            "status": "increased WFDC2 level",
            "notes": "",
            "literature_evidence": "There was a significant difference in the median serum levels of HE4 in breast cancer patients, ovarian cancer patients and healthy volunteers (14.63, 16.47 and 11.52 pmol/l, respectively; P=0.013). No significant differences between the breast cancer and ovarian cancer patient groups was observed, the median serum levels of HE4 in these groups were significantly higher than those in the healthy volunteer group (P=0.006 and P=0.017, respectively).The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4 with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46% [AUC, 0.740 (95% CI, 0.604-0.875), P=0.006] A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer. [PMID:27446579]",
            "loinc_code": "55180-4",
            "tissue": {
                "name": "blood",
                "namespace": "UBERON",
                "id": "0000178",
                "url": "http://purl.obolibrary.org/obo/UBERON_0000178"
            },
            "disease": {
                "disease_id": "DOID:1612",
                "recommended_name": {
                    "id": "DOID:1612",
                    "resource": "Disease Ontology",
                    "url": "http://disease-ontology.org/term/DOID:1612",
                    "name": "breast cancer",
                    "description": "A thoracic cancer that originates in the mammary gland."
                },
                "synonyms": [
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "breast tumor",
                        "description": ""
                    },
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "malignant neoplasm of breast",
                        "description": ""
                    },
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "malignant tumor of the breast",
                        "description": ""
                    },
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "mammary cancer",
                        "description": ""
                    },
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "mammary tumor",
                        "description": ""
                    },
                    {
                        "id": "DOID:1612",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:1612",
                        "name": "primary breast cancer",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "hereditary breast carcinoma",
                        "description": "Breast carcinoma that has developed in relatives of patients with history of breast carcinoma."
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer susceptibility, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, early-onset, susceptibility to, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, invasive ductal, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, lobular, somatic",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, male, susceptibility to, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, protection against, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, somatic",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, susceptibility to, autosomal dominant, somatic mutation",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "familial breast cancer",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "familial breast carcinoma",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "familial cancer of breast",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "familial cancer of the breast",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "hereditary breast cancer",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "hereditary breast carcinoma",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, familial",
                        "description": ""
                    },
                    {
                        "id": "MONDO:0016419",
                        "resource": "MONDO",
                        "url": "https://monarchinitiative.org/disease/MONDO:0016419",
                        "name": "breast cancer, familial Male",
                        "description": ""
                    },
                    {
                        "id": "MIM:114480",
                        "resource": "MIM",
                        "url": "https://www.omim.org/entry/114480",
                        "name": "Breast cancer",
                        "description": "Breast cancer"
                    }
                ]
            },
            "evidence": [
                {
                    "id": "GLY_000625",
                    "database": "GlyGen",
                    "url": "https://data.glygen.org/GLY_000625"
                },
                {
                    "id": "27446579",
                    "database": "PubMed",
                    "url": "https://glygen.org/publication/PubMed/27446579"
                }
            ]
        },
        {
            "best_biomarker_type": "monitoring",
            "status": "increased WFDC2 level",
            "notes": "Measured in serum (UN:0001977) as well.",
            "literature_evidence": "Increases in levels of Human epididymis protein 4 (HE4), Cytokeratin-19 fragment (CYFRA21-1) Carcinoembryonic antigen (CEA), Carbohydrate antigen 125 (CA125), Carbohydrate antigen 153 (CA153), Squamous cell carcinoma antigen (SCC), Carbohydrate antigen 199 (CA199). There were positive associations between levels of C-reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21-1 (R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute lung injuries. [PMID:32347972] SARS-COV-2 infection caused an LDL decrease to occur in the majority of the mild cases; this could be used, in combination with viral RNA detection, as a potential biomarker to facilitate early diagnosis. Serum cancer biomarkers, including CYFRA21-1 and HE4, can be used to monitor the pathological progression of the disease. [DOI:10.2139/ssrn.3552854]",
            "loinc_code": "55180-4",
            "tissue": {
                "name": "blood",
                "namespace": "UBERON",
                "id": "0000178",
                "url": "http://purl.obolibrary.org/obo/UBERON_0000178"
            },
            "disease": {
                "disease_id": "DOID:0080600",
                "recommended_name": {
                    "id": "DOID:0080600",
                    "resource": "Disease Ontology",
                    "url": "http://disease-ontology.org/term/DOID:0080600",
                    "name": "COVID-19",
                    "description": "A Coronavirus infection that is characterized by fever, cough and shortness of breath and that has_material_basis_in SARS-CoV-2."
                },
                "synonyms": [
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "2019 Novel Coronavirus (2019-nCoV)",
                        "description": ""
                    },
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "2019-nCoV infection",
                        "description": ""
                    },
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "Wuhan coronavirus infection",
                        "description": ""
                    },
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "Wuhan seafood market pneumonia virus infection",
                        "description": ""
                    },
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "COVID19",
                        "description": ""
                    },
                    {
                        "id": "DOID:0080600",
                        "resource": "Disease Ontology",
                        "url": "http://disease-ontology.org/term/DOID:0080600",
                        "name": "SARS-CoV-2 infection",
                        "description": ""
                    }
                ]
            },
            "evidence": [
                {
                    "id": "GLY_000625",
                    "database": "GlyGen",
                    "url": "https://data.glygen.org/GLY_000625"
                },
                {
                    "id": "32347972",
                    "database": "PubMed",
                    "url": "https://glygen.org/publication/PubMed/32347972"
                },
                {
                    "id": "10.2139/ssrn.3552854",
                    "database": "DOI",
                    "url": "https://glygen.org/publication/DOI/10.2139/ssrn.3552854"
                }
            ]
        },
        {
            "best_biomarker_type": "prognostic",
            "status": "increased WFDC2 level",
            "notes": "Measured in serum (UN:0001977) as well",
            "literature_evidence": "This is the first report with such a substantial evaluation of cancer biomarkers on a large patient population of COVID-19. Our data demonstrate that levels of serum HE4, CYFRA21-1, CEA, CA125, CA153, SCC, and NSE are positively associated with CRP, a crucial factor in correlation with the severity of the disease. We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19. [PMID:32347972]",
            "loinc_code": "55180-4",
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