MicroRNAs as a potential prognostic factor in gastric cancer

AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR).Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group,n=14,31%) and those who did not (good-prognosis group,n=31,69%).RESULTS:Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P<0.0002,0.0027 and 0.0046 respectively).High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% (13/13).The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION:This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.

Gastric mucin expression in Helicobacter pylori-related, nonsteroidal anti-inflammatory drug-related and idiopathic ulcers

AIM: To determine the pattern of secreted mucin expression in Helicobacter pylori (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers. METHODS: We randomly selected 92 patients with H. pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, andfor mucin 5AC (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the ulcer margin. Inflammation score was assessed according to the Sydney system. RESULTS: MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and absent in the surface epithelium (0%). The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8 ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates. CONCLUSION: Idiopathic ulcers have a unique clinical profile. Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H. pylori and/or NSAID-associated ulcers.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers

AIM:To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori(H.pylori)-associated,non-steroidal inflammatory drug(NSAID)-associated and idiopathic-gastric ulcers.METHODS:We studied a cohort of randomly selected patients with H.pylori(group 1,n=30),NSAID(group 2,n=18),combined H.pylori and NSAID associated gastric ulcers(group 3,n=24),and patients with idiopathic gastric ulcers(group 4,n=20).Immunohistochemistry for MUC1,MUC4,MUC17,and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin(SNA)lectins was performed on sections from the ulcer margins.RESULTS:Staining intensity of MUC17 was higher in H.pylori ulcers(group 1)than in idiopathic ulcers(group4),11.05±3.67 vs 6.93±4.00 for foveola cells,and10.29±4.67 vs 8.00±3.48 for gland cells,respectively(P<0.0001).In contrast,MUC1 expression was higher in group 4 compared group 1,9.89±4.17 vs 2.93±5.13 in foveola cells and 7.63±4.60 vs 2.57±4.50 for glands,respectively(P<0.0001).SNA lectin staining was increased in group 4,in parallel to elevated MUC1expression,indicating more abundantα2-6 sialylation in that group.CONCLUSION:Cytoplasmic MUC17 staining was sig-nificantly decreased in the cases with idiopathic ulcer.The opposite was observed for both MUC1 and SNA lectin.This observation may reflect important pathogenic mechanisms,since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.