Anti-tNASP antibodies as a diagnostic marker for malignant tumors

Abstract

Background: Nuclear Autoantigenic Sperm Protein (NASP), a facilitator of chromatin assembly, is expressed as two splice variants: tNASP, specific for testis and cancer cells, and sNASP, expressed in all somatic cells. Exposure of tNASP to the immune system induces a robust humoral immune response. We suggested that patients with malignancies have a higher level of serum anti-tNASP antibodies than those without malignancies. We hypothesized that detection of anti-tNASP antibodies in serum can be used as a cancer screening test. Methods: Sera from cancer patients and healthy individuals (negative control) were tested for the presence of antibodies against tNASP using enzyme-linked immunosorbent assay (ELISA) with a recombinant tNASP fragment as bait. A total of 139 serum samples from patients with a known malignancy were tested. These included bladder (11), brain (12), breast (12), endometrial (10), gastrointestinal (10), lung (10), ovarian (10), prostatic (12), skin (10), soft tissue (12), thyroid (10), or urinary (10) malignancy, as well as sera from 10 control patients with no known cancers (negative control). Results: The majority of samples (56.5%) demonstrated elevated levels of anti-tNASP antibodies compared to negative control: glioblastoma, astrocytoma, colorectal adenocarcinoma, pulmonary adenocarcinoma, large-cell and squamous cell lung carcinoma, ovarian serous carcinoma, ovarian adenocarcinoma, bladder urothelial and squamous cell carcinoma, adenocarcinoma of the urinary bladder, prostate adenocarcinoma, and endometrial adenocarcinoma. Samples from patients with melanoma, renal, thyroid, breast carcinomas, and different types of sarcomas demonstrated similar levels of antitNASP antibodies as control samples. Conclusions: Serum anti-tNASP antibody levels are markedly elevated in the majority of cancer patients tested as compared to healthy controls. These data demonstrate that detection of anti-tNASP antibodies is a viable diagnostic approach and has the potential to be used as an early noninvasive screening method for detection of multiple cancers.