Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat

<p>Abstract</p> <p>Background</p> <p>There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model.</p> <p>Results</p> <p>Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory.</p> <p>In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. <b>Conclusions</b>: We found an increase in core-α-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.</p

Serum N-glycan profile shift during human ageing.

Biomarkers indicating biological age are of significant interest for prevention, diagnosis and monitoring (and the treatment) of age-related diseases. We previously reported an alteration of serum N-glycan profile in old humans using "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA-FACE). To validate the shift in serum N-glycan profile during ageing, we studied serum N-glycan profiles in different age groups of healthy volunteers, patients with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder involving neurodegeneration and premature ageing. We found that the log of the ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to the age of 40years and thereafter gradually increased to reach its highest level in nonagenarians. Patients with dementia or Cockayne syndrome had a higher GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be used as a non-invasive surrogate marker for general health, for forecasting disease progression during ageing, and for monitoring the efficacy of anti-ageing food compounds