Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: A monocentric cohort study in China

Abstract

BackgroundThe search for better non-invasive biomarkers for gastric cancer remains ongoing. We investigated the predictive power of serum trefoil factor (TFF) levels as biomarkers for gastric cancer in comparison with the pepsinogen (PG) test.MethodsPatients with gastric cancer, chronic atrophic gastritis (CAG) or chronic non-atrophic gastritis (CNAG), and healthy people were recruited. Serum concentrations of TFFs, PG I, and PG II, as well as the presence of antibodies against Helicobacter pylori, were measured by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristics (ROC) were used to compare the predictive powers of the selected factors.ResultsThe serum concentrations of TFF1, TFF2, and TFF3 in the control groups were significantly lower than those in the gastric cancer group with the exception of TFF2 which was elevated in CAG. The area under the ROC curve for TFF3 was greater than that for the PG I/II ratio (0.81 vs 0.78). TFF3 also had a significantly higher predictive power for distinguishing gastric cancer than the PG test (odds ratio: 10.33 vs 2.57). Moreover, combining the serum TFF3 and PG tests for gastric cancer had better predictive power than either alone.ConclusionsSerum TFF3 may be a better predictor of gastric cancer than the PG test, while the combined testing of serum PG and TFF3 could further improve the efficacy of gastric cancer screening.

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…significantly differ among different histological types or TNM stages [93]. The concentration of serum TFF2 in patients with intestinal type GC is remarkably lower than that in diffuse type, but it has no distinction between early and advanced stages of GC [93].…”

“…The concentration of serum TFF2 in patients with intestinal type GC is remarkably lower than that in diffuse type, but it has no distinction between early and advanced stages of GC [93]. The concentration of serum TFF3 is also significantly lower in patients with intestinal type than diffuse type GC, and it is reduced in patients with early GC than in those advanced GC [63,93].…”

“…Although there are no direct evidences, it is possible that the ectopic expression of TFF3 in intestinal metaplasia of the stomach could induce the spillage of TFF3 into the bloodstream, and this could elevate serum TFF3 levels [92]. However, the origin of high serum TFFs also needs further investigation [93].…”

“…In serum TFFs and pepsinogen tests, only serum TFF3 levels were not pronouncedly affected by Hp eradication, suggesting that serum TFF3 could be a stable biomarker of GC risk even after Hp eradication [91]. And using barium X-ray examination, Hp antibody testing, serum PG testing, serum TFF3 testing or a combination of serum PG and TFF3 testing to screen GC has a gradually increasing efficiency [75,92,93]. In addition, the sensitivity of the combination of TFF3 and PG testing in intestinal-type adenocarcinoma is higher than that in diffuse-type adenocarcinoma [92].…”

Etiology and Prevention of Gastric Cancer

“…Gastrin-17 has been also considered as a biomarker for antral atrophy [78,79]. Trefoil factor 3, a small and stable molecule secreted by the gastrointestinal tract, has been shown to be a better biomarker for both atrophy and gastric cancer than pepsinogens [80,81]. In addition, anti-gastric parietal cell antibodies have been considered as independent biomarkers for gastric atrophy [82].…”