Serum Antibodies to Huntingtin Interacting Protein-1: A New Blood Test for Prostate Cancer

Abstract

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1 null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-A-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer. (Cancer Res 2005; 65(10): 4126-33)

Beyond prostate-specific antigen: alternate serum markers

“…Antibody array profiling has also identified possible serum markers, such as thrombospondin-1, that may differentiate between benign and malignant disease. 141 Increased antibody titers of antiproteasome and anti-huntingtin interacting protein-1 have been associated with the presence of CaP, 142,143 and a serum ELISA against the latter yielded a specificity of 97% when combined with an anti-AMACR test. Other autoantibody signatures may increase the discriminatory power of a screening test and are currently being evaluated.…”

New circulating biomarkers for prostate cancer

“…100 Other autoantibodies to antigens expressed in PCa (huntington-interacting protein 1, protasomes) have also been detected and it has been reported that their combination could improve the screening performance reaching a specificity of 97%. 101 Recently, using a so-called 'immunomics' technique, Wang et al 102 analyzed the overall humoral response against specific tumoral antigens in PCa and were able to identify multiple antigens. With this panel of autoantibodies, they could detect PCa with a sensitivity of 81.6% and a specificity of 88.2%, which was more accurate than PSA alone.…”

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

“…Simultaneous quantification of autoantibodies and PSA was proposed as a new approach to improve diagnosis and prognosis of prostate cancer (5). After autoantibodies against Huntingtin interacting protein-1 were identified in prostate cancer patients, combining serum reactivity with PSA values led to a screening discrimination with 97% specificity (6).…”