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Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.

ABSTRACT: Improving methods for early detection of gastric cancer could reduce mortality. Measurements of serum pepsinogen levels have been used for screening in Japan without satisfactory levels of sensitivity or specificity. Trefoil factor family (TFF) proteins (TFF1, TFF2, and TFF3) are small and stable molecules secreted by the mammalian gastrointestinal tract. Foveolar hyperplasia, spasmolytic polypeptide (TFF2)-expressing metaplasia, and intestinal metaplasia are histologic changes observed in patients with atrophic gastritis; they express TFF1, TFF2, and TFF3, respectively. We investigated whether serum levels of TFF can be used as markers for gastric cancer screening.Serum was collected from 183 patients with gastric cancer and 280 healthy individuals without cancer. Serum levels of anti-Helicobacter pylori immunoglobulin G, pepsinogen I, pepsinogen II, TFF1, TFF2, and TFF3 were measured by enzyme-linked immunosorbent assay and associated with gastric cancer.Using a cutoff of 3.6 ng/mL, the level of TFF3 was significantly increased in serum samples from patients with cancer (odds ratio, 18.1; 95% confidence interval, 11.2-29.2); using this test, patients with cancer were identified with 80.9% sensitivity and 81.0% specificity. The test for TFF3 had a significantly higher odds ratio than that for pepsinogen. A test for the combination of TFF3 and pepsinogen had better results than the test for only pepsinogen.Serum levels of TFF3 are a better marker of gastric cancer than pepsinogen; a test for the combined levels of serum pepsinogen and TFF3 could improve gastric cancer screening.

SUBMITTER: Aikou S

PROVIDER: S-EPMC3163741 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.

Aikou Susumu S Ohmoto Yasukazu Y Gunji Toshiaki T Matsuhashi Nobuyuki N Ohtsu Hiroshi H Miura Hirona H Kubota Kensuke K Yamagata Yukinori Y Seto Yasuyuki Y Nakajima Atsushi A Goldenring James R JR Kaminishi Michio M Nomura Sachiyo S

Gastroenterology 20110527 3

<h4>Background & aims</h4>Improving methods for early detection of gastric cancer could reduce mortality. Measurements of serum pepsinogen levels have been used for screening in Japan without satisfactory levels of sensitivity or specificity. Trefoil factor family (TFF) proteins (TFF1, TFF2, and TFF3) are small and stable molecules secreted by the mammalian gastrointestinal tract. Foveolar hyperplasia, spasmolytic polypeptide (TFF2)-expressing metaplasia, and intestinal metaplasia are histologic ...[more]

PMID: 21699780

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Project description:ObjectivesTrefoil factor 3 (TFF3) is a small peptide that plays an important role in mucosal protection, cell proliferation, and cell migration. The aberrant expression of TFF3 is correlated with gastrointestinal inflammation, solid tumors, and other clinical diseases. The objective of this study was to identify the distribution characteristics of serum TFF3 in common clinical diseases.Materials and methodsA large prospective randomized study of 1,072 Chinese patients was performed using an enzyme-linked immunosorbent assay (ELISA) to examine the serum TFF3 concentrations in patients with different diseases. A matched case-control study was conducted on patients with chronic kidney disease (CKD) stages 1-5. Immunohistochemistry (IHC) was performed using renal tissues to determine the relationship between the severity of CKD and the serum and urine concentrations of TFF3 peptides.ResultsThe mean serum concentrations of TFF3 in patients with CKD, metastatic and secondary carcinoma (MC) and acute gastroenteritis (AG) (200.9 ng/ml, 95.7 ng/ml and 71.7 ng/ml, respectively) were significantly higher than those in patients with other common clinical diseases. A positive correlation tendency was observed between the serum TFF3 concentrations and the severity of CKD. The mean serum TFF3 values for CKD stages 1-5 were 23.6 ng/ml, 29.9 ng/ml, 54.9 ng/ml, 85.0 ng/ml and 176.6 ng/ml, respectively. The same trend was observed in the urine TFF3 concentrations and the CKD stages. The creatinine(Cr)-corrected concentrations of TFF3 in urine were 367.1 ng/mg·Cr, 910.6 ng/mg·Cr, 1,149.0 ng/mg·Cr, 1,610.0 ng/mg·Cr and 3,475.0 ng/mg·Cr for CKD stages 1-5, respectively. IHC revealed that TFF3 expression was concentrated in tubular epithelial cells.ConclusionsThe influence of kidney injuries must be fully considered when performing clinical TFF3 research. Further studies on TFF3 in CKD will contribute to our understanding of its pathological roles and mechanisms in other diseases.

Project description:Trefoil factor family member 2 (Tff2) is significantly involved in intestinal tumor growth in ApcMin/+ mice, which can be used as a human colon cancer model. TFF2, which encodes TFF2 (spasmolytic protein 1) is highly expressed in human cancer tissues, including the pancreas, colon and bile ducts, as well as in normal gastric and duodenum tissues. By contrast, TFF2 exhibits low expression levels in other normal tissues, including the small and large intestine. Furthermore, TFF2 expression has not been detected in DLD-1 cells, a cell line derived from human colon cancer. The trigger of TFF2 expression in normal and tumor cells remains unknown. Highly malignant tumor tissues are characterized by higher temperatures and lower pH (6.2-6.9) than in normal tissues, where the normal pH ranges from 7.2 to 7.4. This microenvironment exacerbates malignancy by promoting the acquisition of cell death resistance, drug resistance and immune escape. Therefore, the present study examined how TFF2 expression is affected in cultured cells that imitate the tumor tissue microenvironment. The incubation temperature was increased from 37 to 40˚C, but no expression of TFF2 was induced. Subsequently, a culture solution with an acidic pH was prepared to simulate the Warburg effect in tumors. TFF2 expression was increased by 42.8- and 5.8-fold in cells cultured in acidic medium at pH 6.5 and 6.8 compared with at pH 7.4, respectively, as determined using the relative quantification method following quantitative polymerase chain reaction. The present study also analyzed fluctuations in the expression levels of genes other than TFF2, under acidic conditions. Acidic conditions upregulated the expression of genes related to cell membranes and glycoproteins, based on the Database for Annotation, Visualization, and Integrated Discovery. In conclusion, TFF2 was highly expressed under acidic conditions, implying that it may have an important function in protecting the plasma membrane from acidic environments in both normal and cancer cells. These findings warrant further investigation of TFF2 as a target of cancer therapy and diagnosis.

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Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.

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Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.

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