The role of hyaluronan modification in the etiopathogenesis of gastric cancer.

Abstract

Objective: Gastric cancer is the second most common cancer in the world, accounting for 650,000 deaths per year, and is observed in approximately 10% of the patients diagnosed. Extracellular matrix abnormalities have been documented in gastric cancer patients. The aim of our study was to understand the role of high levels of hyaluronan, an extracellular matrix glycosaminoglycan, and its mechanistic role in gastric cancer pathobiology.

Methods: Blood samples were collected from 82 gastric cancer patients and 41 healthy volunteers. Hyaluronan measurements were performed with the help of commercially purchased enzyme-linked immunosorbent assay kits. Gastric cancer (n=27) and healthy (n=29) tissue specimens were obtained after surgery and aliquoted for Western blot, immunofluorescence, and messenger RNA expression analysis.

Results: Increased hyaluronan levels were detected in the blood of cancer patients compared to controls [plasma hyaluronan levels mg/dL (mean±SD): gastric cancer (n=82) 549.80±155.68, and healthy control (n=41) 27.21±4.95 (p<0.044)]. In addition, intense hyaluronan binding protein staining was observed in gastric cancer tissues, while tumor necrosis factor-inducible gene 6 messenger RNA expression was found to be significantly increased in gastric cancer tissues compared to healthy controls [tumor necrosis factor-inducible gene 6 messenger RNA expression: gastric cancer (n=27) 7.09±1.94 and healthy control (n=29) 3.20±0.67 (p=0.048)] according to the immunofluorescence staining.

Conclusion: The high hyaluronan levels in gastric cancer patients and the detection of increased messenger RNA levels of the tumor necrosis factor-inducible gene 6 enzyme in gastric cancer tissue, supporting a possible hyaluronan modification, suggest that this abnormality may have an important role in the formation of gastric cancer.