Influence of Helicobacter pylori status and eradication on the serum levels of trefoil factors and pepsinogen test: serum trefoil factor 3 is a stable biomarker.
OBJECTIVE
Emerging data indicate that serum trefoil factors (TFFs), especially TFF3, could be potential biomarkers for gastric cancer risk. We aimed to evaluate the influence of Helicobacter pylori (H. pylori) status and eradication on serum TFFs and the pepsinogen test.


METHODS
Healthy individuals who underwent a thorough medical checkup were enrolled in study 1, and gastric ulcer patients who undertook H. pylori eradication therapy were enrolled in studies 2 and 3. Serum levels of the TFFs (TFF1, TFF2 and TFF3), H. pylori antibody and pepsinogen test were examined in all studies. In study 3, TFF expressions in biopsy samples of the gastric mucosa were additionally examined before and 2 months after eradication.


RESULTS
In 1,260 healthy individuals enrolled in study 1, serum TFF1 and TFF2 levels were markedly different between H. pylori antibody-positive and -negative participants (P < 0.0001). Differences in serum TFF3 levels between H. pylori antibody-positive (5.85 ± 3.93 ng/ml) and -negative subjects (5.27 ± 2.38 ng/ml) were statistically significant (P = 0.002) but small in absolute value. In 178 gastric ulcer patients enrolled in study 2, serum TFF1, TFF2 and positive rates of the pepsinogen test significantly decreased 2 months after H. pylori eradication therapy (P < 0.001). In contrast, serum TFF3 levels and positive rates of high TFF3 levels (≥7 ng/ml) did not significantly change with H. pylori-eradication until 5 years after eradication. In 18 gastric ulcer patients (study 3), TFF1 and TFF2 were mainly expressed in the foveolar epithelium, and TFF2 was additionally expressed in the pyloric glands. These expressions significantly decreased with H. pylori eradication. TFF3s were scarcely expressed in the gastric mucosa except in goblet cells of intestinal metaplasia, which did not change with H. pylori eradication.


CONCLUSIONS
In serum TFFs and pepsinogen tests, only serum TFF3s were not significantly affected by H. pylori eradication, suggesting that serum TFF3 could be a stable biomarker of gastric cancer risk even after H.pylori eradication in contrast with the pepsinogen test.
Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. kaise@toranomon.gr.jp
Mitsuru
M
Kaise
Jun
J
Miwa
Ai
A
Fujimoto
Jun
J
Tashiro
Daisuke
D
Tagami
Hiromi
H
Sano
Yasukazu
Y
Ohmoto
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000097:blood*; D010455:Peptides / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins / Q000097:blood
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D010435:Pepsinogens; D010455:Peptides; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins