Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Gastric Cancer. 2013 Jul;16(3):329-37. doi: 10.1007/s10120-012-0185-y. Epub 2012 Aug 21.
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.
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.
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.
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.
新出现的数据表明,血清三叶因子(TFFs),尤其是 TFF3,可能是胃癌风险的潜在生物标志物。本研究旨在评估幽门螺杆菌(H. pylori)状态和根除对血清 TFFs 和胃蛋白酶原检测的影响。
在研究 1 中,纳入了接受全面体检的健康个体;在研究 2 和研究 3 中,纳入了接受 H. pylori 根除治疗的胃溃疡患者。所有研究均检测了 TFFs(TFF1、TFF2 和 TFF3)、H. pylori 抗体和胃蛋白酶原检测的血清水平。在研究 3 中,还在根除治疗前和 2 个月后检测了胃黏膜活检样本中的 TFF 表达。
在研究 1 中,纳入了 1260 名健康个体,H. pylori 抗体阳性和阴性参与者的血清 TFF1 和 TFF2 水平差异有统计学意义(P<0.0001)。H. pylori 抗体阳性(5.85±3.93ng/ml)和阴性(5.27±2.38ng/ml)受试者的血清 TFF3 水平差异有统计学意义(P=0.002),但绝对值较小。在研究 2 中,纳入了 178 名胃溃疡患者,H. pylori 根除治疗 2 个月后,血清 TFF1、TFF2 和胃蛋白酶原检测的阳性率显著下降(P<0.001)。相反,血清 TFF3 水平和高 TFF3 水平(≥7ng/ml)的阳性率在根除后 5 年内与 H. pylori 根除无显著变化。在 18 名胃溃疡患者(研究 3)中,TFF1 和 TFF2 主要在小凹上皮表达,TFF2 还在幽门腺表达。这些表达随着 H. pylori 的根除而显著下降。TFF3 在胃黏膜中表达甚少,除了肠化生的杯状细胞外,与 H. pylori 的根除无关。
在血清 TFFs 和胃蛋白酶原检测中,只有血清 TFF3 不受 H. pylori 根除的显著影响,这表明与胃蛋白酶原检测相比,血清 TFF3 即使在 H. pylori 根除后也可能是胃癌风险的稳定生物标志物。