Diagnostic Assays : Cancer


Blood Protein Biomarkers for Detection of Colon Cancer

UW–Madison researchers have developed methods and kits for diagnosing colon cancer, including precancerous and early stage disease, using protein biomarkers in blood/serum. Approximately 30 peptides identified and validated in animal models were used to conduct targeted proteomic analysis in humans. The serum levels of several of the biomarkers correlated with cancer incidence and outcomes in the study of normal patients versus those with stage 1, 2 or stage 3 colon cancer.

Biomarkers for Detecting Prostate Cancer

UW–Madison researchers have identified eight genetic markers, or biomarkers, for prostate cancer. They can be detected in histologically normal prostate samples and/or the bodily fluids of men with no history of prostate cancer.

The biomarkers act as red flags, exhibiting abnormal methylation levels when cancer is present in peripheral prostate tissue (this is called cancer ‘field defect’). These changes are believed to represent early stages of the cancer process.

The biomarkers are associated with the genes CAV1, EVX1, MCF2L, FGF1, WNT2, NCR2, EXT1 and SPAG4.

Detecting Ovarian Cancer and Risk

A UW–Madison researcher and others have developed a new ovarian cancer screening method that measures total or ionized serum calcium levels in blood samples. Women exhibiting elevated levels may be up to three times more likely to be diagnosed with ovarian cancer.

Serum calcium can be detected and quantified using standard techniques, including absorption spectrometry, ion selective electrode, fluorescent detection, etc. The measured levels can be incorporated into an overall risk score, identifying women who should undergo further CA125 and ultrasound screening.

Muc16 Bound to Immune Cells Provides an Improved Indicator for Ovarian Cancer and Preeclampsia

UW-Madison researchers now have discovered a new prognostic and diagnostic indicator for ovarian cancer and preeclampsia.   CA125 is a peptide epitope from a large glycosylated protein called Mucin 16 (Muc16).  The researchers found that levels of Muc16 bound to immune cells provide a more specific indicator of ovarian cancer regression or recurrence.  Because Muc16 binds to specific subsets of immune cells that express Siglec-9, measuring the amount of Siglec-9 expressed on the immune cells also provides a method of detecting ovarian cancer. 

In addition, Muc16 and Siglec-9 may serve as indicators of preeclampsia in pregnant women.  They can be used to detect preeclampsia and to distinguish women with ovarian cancer from healthy pregnant women and women with preeclampsia.

HPV-Positive Biomarkers for Cervical and Head and Neck Cancers

UW-Madison researchers have identified three potential biomarkers that are specific for HPV-positive cancers in cervical and head and neck tumors: testicular cell adhesion molecule 1 (TCAM1), synaptonemal complex protein 2 (SYCP2) and stromal antigen 3 (STAG3).  These biomarkers can be used to detect cervical or head and neck cancer.  TCAM1 and SYCP2 also can be used to detect precancerous lesions.

TCAM1, SYCP2 and STAG3 are testis-specific human genes.  The inventors have shown that mRNA from these genes is expressed in HPV-positive head and neck and cervical cancers but cannot be detected in normal somatic tissues or HPV-negative head and neck cancers.

Additionally, the TCAM1 protein likely is expressed on the cell surface, which would make it an accessible, easily-assayed biomarker for HPV-positive cells in cancers and precancerous lesions.  TCAM1 also may provide a useful target for therapies against HPV-positive cancers and precancerous lesions.

Prostate Cancer and Melanoma Screening

UW-Madison researchers have developed a minimally invasive method of screening for prostate cancer or melanoma. They identified a number of antigens to which patients with prostate cancer or melanoma have developed antibody immune responses. The antigens may provide clinicians with new tools for the diagnosis and monitoring of prostate cancer or melanoma. A blood sample from a patient can be tested against a panel of the prostate cancer or melanoma antigens. An immune reaction to any member of the panel might indicate the patient needs further examination.

The researchers also developed a method for determining if an anti-cancer immune therapy is effective. Anti-tumor vaccines stimulate the immune system to form antibodies against tumor cells, delaying the onset or progression of cancer. The panel of antigens can be used to determine if an immune therapy, either antigen-specific or non-antigen-specific, has elicited responses to other antigens and might therefore be an effective therapy. In addition, the antigens themselves may serve as targets for antigen-specific immune therapies.

Early Detection of Hemangiosarcoma and Angiosarcoma

UW-Madison researchers have developed a simple, sensitive and specific test for detecting hemangiosarcoma in its early stages in dogs at risk. The inventors discovered that the “primitive” endothelial cells associated with hemangiosarcoma or angiosarcoma, a similar tumor that affects humans, express a specific combination of proteins on their surface. To diagnose hemangiosarcoma or angiosarcoma, multiparameter flow cytometry can be used to detect cells that express these proteins.

hMREII Antiserum for the Detection of DNA Damage

A UW-Madison researcher has now isolated such a homolog by using a two-hybrid system to determine which proteins interact with the repair enzyme, DNA ligase I. The gene, termed hMREII, maps to human chromosome 11q21 in a region frequently associated with cancer-related chromosomal abnormalities.

The researcher cloned a 1900 base pair portion of the hMREII gene into a bacterial expression vector and used the bacterially produced and purified hMREII to immunize rabbits. The resulting antiserum detects the hMre11 protein, which has been shown to associate with radiation-induced double stranded DNA breaks, as well as human telomeres. Congenitally acquired defects in hMre11 and its binding partner, Nbs1, result in cancer predisposition and ionizing radiation sensitivity; in these diseases, the localization of hMre11 to DNA breaks is compromised. Thus, the antiserum is useful for detecting DNA damage and assessing the functional status of hMre11 and its associated proteins. The Mre11 complex, consisting of these proteins, is a central mediator of DNA damage responses in all eukaryotic cells.