Today, PSA
is the only biomarker used in daily practice for diagnosis and in follow-up of prostate cancer patients. Although recent improvements in imaging by multimodality MRI and PET/CT scan, we lack a sensitive method to detect lymph node metastases in prostate cancer patients. Surgical lymph node dissection is still golden standard thus new markers to predict increase risk of lymph node metastases are highly warranted. Our study therefore suggests investigating CNDP1 further using functional analysis to elucidate, which mechanisms contribute to its decreasing plasma levels and how such changes can be addressed by therapy. Hereby, a focus could be on lymphatic systems and its contribution to decreases of CNDP1, but it will also be required to assess whether this is a check details prostate or gender specific finding. There were a few number of N1 cases in the analyzed cohorts, so further
replication in independent sample collections and cohorts is GSKJ4 anticipated to confirm the observed relation of CNDP1 to advanced PCa. We had previously speculated on the influence of glycosylation status on CNDP1 detection [5]. It is known that carbohydrate components of glycoproteins perform critical biological functions in protein sorting, immune and receptor recognition, inflammation, pathogenicity, metastasis, and other cellular processes [16]. N-glycans may play a role in cancer progression, as malignant cells have been shown to synthesize longer chains of N-glycans [17] and [18] and alterations of specific glycans have been observed in metastatic prostate cancer [19]. Using antibody-based detection in combination
with plasma and recombinant protein being subjected to enzymatic deglycosylation, we could not find that eltoprazine indications of CNDP1 level decrease were primarily effected by their state of glycosylation. Further analysis would be required to better understand CNDP1 glycosylation in prostate cancer, but our current data did not support previous speculations, as differential detection of CNDP1 appeared unrelated to glycosylation. Also, the relation of detected protein levels where corroborated for off-target detection. First for CNDP2, a peptidase found as a cytosolic homodimer with 2 acetylation sites and has recently been found in proteomic analysis of Parkinson’s disease [20]. CNDP2 has a 55% sequence similarity to CNDP1 but as shown by the panel of applied capture antibodies, our data did not reveal that CNDP2 would be detected instead of CNDP1. The highly abundant protease inhibitor A2M, which can form a stable complex with CNDP1, was hypothesized to constitute the approximately 150 kDa protein band observed with WB using HPA-1, HPA-1.F15 and CAB-1, as A2M or A2M-CNDP1. The interaction between A2M and anti-CNDP1 HPA-1, CAB-1, MAB-1.1 and MAB-1.2 were studied using sandwich assays.