Alterations in the Serum Glycome Due to Metastatic Prostate Cancer

Abstract

Glycomic profiles derived from human blood sera of 10 healthy males were compared to those from 24 prostate cancer patients. The profiles were acquired using MALDI-MS of permethylated N-glycans released from 10-microL sample aliquots. Quantitative permethylation was attained using solid-phase permethylation. Principal component analysis of the glycomic profiles revealed significant differences among the two sets, allowing their distinct clustering. The first principal component distinguished the 24 prostate cancer patients from the healthy individuals. It was determined that fucosylation of glycan structures is generally higher in cancer samples (ANOVA test p-value of 0.0006). Although more than 50 N-glycan structures were determined, 12 glycan structures, of which six were fucosylated, were significantly different between the two sample sets. Significant differences were confirmed through two independent statistical tests (ANOVA and ROC analyses). Ten of these structures had significantly higher relative intensities in the case of the cancer samples, while the other two were less abundant in the cancer samples. All 12 structures were statistically significant, as suggested by their very low ANOVA scores (<0.001) and ROC analysis, with area under the curve values close to 1 or 0. Accordingly, these structures can be considered as cancer-specific glycans and potential prostate cancer biomarkers. Therefore, serum glycomic profiling appears worthy of further investigation to define its role in cancer early detection and prognostication.

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

“…Recently, we have shown that fucosylation of PSA can be used to differentiate aggressive from nonaggressive prostate cancer (37). Altered fucosylated glycans have been reported in the serum glycome from 10 normal patients and 24 prostate cancer patients (38). However, the cause of the glycan changes was not clear in the previous reports.…”

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

“…Another study showed that inhibition of the glycosylation of EGFR and Met in glioma cells could significantly reduce the tumor growth, leading to an enhancement in tumor radiosensitivity [28]. Meanwhile, there are also many other high-throughput studies performed in efforts to find new markers of glycoproteins in various cancers [29][30][31]. All these researches have provided new insights into understanding the progression of cancer and possible markers for clinical application.…”

Microfluidic integration for automated targeted proteomic assays

“…Proteomic studies suggest a promising link between prostate cancer incidence and differential isoform expression in healthy and cancer patient sera (6,8,9). Although promising, rigorous validation studies are needed to translate the potential of protein isoforms to the clinic.…”

“…Recent ELISA-based formats offer notable gains in analytical sensitivity (10,11). Nevertheless, mounting evidence suggests that protein isoform "fingerprinting" could advance diagnostic performance (6,9,12). Unfortunately, ELISA is severely limited for isoform discrimination because antibodies specific to protein isoforms often do not exist (12).…”