DIAGNOSTIC ALGORITHMS FOR DETERMINING AND TREATING CLINICALLY SIGNIFICANT PROSTATE CANCER BASED ON SIALYLATED AND FUCOSYLATED PROSTATE SPECIFIC ANTIGEN

Smart overview of the Invention

Prostate cancer (PCa) is a prevalent form of cancer among men, ranking as the second most commonly diagnosed cancer and the fifth leading cause of cancer-related deaths. The prostate-specific antigen (PSA) test is widely used for screening, but its lack of specificity can lead to misdiagnosis and unnecessary treatments. Elevated PSA levels can arise from various conditions, resulting in a high false positive rate that complicates diagnosis and often leads to invasive procedures like needle biopsies, which carry significant risks.

Alterations in PSA Glycosylation

Research indicates that aberrant protein glycosylation is a characteristic of many cancers, including prostate cancer. The glycosylation patterns of PSA differ notably between cancerous and normal prostate cells, with changes in the levels of specific sialic acid linkages. These altered glycosylation patterns provide potential biomarkers for distinguishing clinically significant prostate cancer from benign conditions or low-risk disease.

Diagnostic Methods Using PSA Glycosylation

The patent introduces methods for measuring the relative amounts of α2-3-linked and α2-6-linked N-acetylneuraminic acid on PSA in blood serum or plasma samples. By employing electrospray ionization mass spectrometry (ESI-MS) and center-of-mass analysis, these methods can help classify patients into risk categories for prostate cancer, ranging from low risk (GG1) to high risk (GG3-5). The fractional content of α2-3-linked Neu5Ac plays a crucial role in this classification.

Guidelines for Biopsy Recommendations

Based on the quantification of α2-3-linked Neu5Ac, specific guidelines are established for recommending needle biopsies. If the fraction exceeds 28%, a biopsy is advised without additional imaging. Conversely, if it's below 24%, no biopsy is recommended. For values between 24% and 28%, further assessment of fucosylated PSA is necessary to determine the need for biopsy or MRI scans.

Post-Surgery Monitoring and Treatment Methods

The invention also provides strategies for monitoring patients post-prostate cancer surgery. If the α2-3-linked Neu5Ac fraction is greater than 28%, additional treatment is recommended. For fractions between 24% and 28%, intensified monitoring is advised, while fractions below 24% indicate no further monitoring is needed. These methods aim to enhance patient management by tailoring interventions based on specific biomarker measurements.