Abstract / Summary
ABSTRACT Gastrointestinal (GI) tumors represent a significant global health burden, necessitating robust strategies for early detection. However, the clinical utility of conventional protein biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 19‐9 (CA19‐9) in early diagnosis is restricted by insufficient sensitivity and specificity. In contrast, trefoil factor 3 (TFF3) is aberrantly expressed in GI tumors and holds potential as a GI tumor marker. This study enrolled 966 subjects and systematically evaluated the diagnostic performance of plasma TFF3, both independently and in combination with existing biomarkers, for gastric cancer (GC) and pan‐GI cancer. Results indicated significantly elevated plasma TFF3 levels in GC patients compared to healthy individuals ( p < .0001). In the GC cohort, a diagnostic panel combining TFF3, CEA, Pepsinogen I, Pepsinogen II, Gastrin‐17, age, and sex achieved an area under the curve (AUC) of 0.846. Furthermore, TFF3 demonstrated notable diagnostic efficacy across pan‐GI cancers. The AUC for differentiating between healthy control (HC) and colorectal cancer (CRC), esophageal cancer (EC), pancreatic cancer (PC), hepatocellular carcinoma (HCC), or pan‐GI cancer was 0.664, 0.774, 0.696, 0.714, and 0.741, respectively. Notably, combining TFF3 with CEA and baseline characteristics significantly improved the diagnostic performance in pan‐GI cancer, with an AUC of 0.825 and 0.816 in GC + EC and GC + EC + CRC respectively. These findings validated and clarified that plasma TFF3, in combination with different other markers such as gastric function indicators and CEA, holds promise as a biomarker for early screening and early diagnosis of GC and pan‐GI tumors, respectively.