Serum Trefoil Factor 3 as a Protein Biomarker for the Diagnosis of Colorectal Cancer

Abstract

Colorectal cancer is one of the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for timely diagnosis and effective treatment. Our aim in the present study was to detect the serum level of trefoil factor 3 protein and evaluate the diagnostic accuracy of trefoil factor 3 in patients with colorectal cancer. We collected serum samples from 204 participants (127 patients with colorectal cancer, 35 patients with polyps, and 42 healthy controls). The levels of serum trefoil factor 3 and carcinoembryonic antigen expression were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to calculate the diagnostic accuracy of trefoil factor 3 in patients with colorectal cancer. The serum levels of trefoil factor 3 in patients with colorectal cancer (6.66 + 2.4 ng/mL; P < .00l) and polyps (3.86 + 1.3 ng/mL; P < .00l) were significantly increased compared to healthy controls (2.09 + 1.0 ng/mL). Moreover, the area under the receiver operating characteristic curve for trefoil factor 3 was greater than carcinoembryonic antigen (0.889 vs 0.715). At a cutoff value of 5.591 ng/mL, the diagnostic sensitivity, specificity, and likelihood ratio of serum trefoil factor 3 for colorectal cancer was 74.2%, 94.8%, and 14.25, respectively. Furthermore, the serum trefoil factor 3 levels in early colorectal cancer (TNM stage I, 3.67 + 1.27 ng/mL) were significantly increased compared to healthy controls (P < .001); however, there was no significant difference compared to patients with polyps (P ¼ .576). We observed that the serum trefoil factor 3 levels decreased after surgery (6.66 + 2.4 vs 4.48 + 1.80 ng/mL; P < .001). In addition, high serum trefoil factor 3 levels were associated with poor tumor differentiation and clinical TNM stage (P < .05). In conclusion, serum trefoil factor 3 is a promising biomarker for the diagnosis of colorectal cancer and prognosis of patients.

Systematic review of blood diagnostic markers in colorectal cancer

“…In this category, the more promising proteins were trefoil factor (TFF)3 [ 21 ], CA11-19 [ 22 ], a combination of insulin-like growth factor binding protein 2 (IGFBP2), Dickkopf-3(DKK3), and pyruvate kinase M2 (PKM2) [ 23 ] and DC-SIGN/DC-SIGNR [ 24 ].…”

“…It is thought to promote invasion of cells by acting directly on the cells and indirectly on the vasculature. Results from the study by Li et al showed a sensitivity of 74.2% and specificity of 94.8%; however, the level of this marker in polyps is not significantly different from that in the CRC cohort, making this less likely to be a useful diagnostic test [ 21 ].…”

Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer

“…To discover urinary diagnostic biomarkers for CRC, we thoroughly searched the previous literature on serum protein biomarkers for the diagnosis of CRC using PubMed, and identified 6 small protein biomarker candidates with a high AUC and high accuracy: Cyr 61, TFF3, IGFBP3, ANGPTL2, SERPINA1 and EFEMP2 [15], [16], [17], [18], [19], [20]. Based on the results from the literature search, we analyzed urinary protein concentrations of these 6 proteins in the training cohort, using quantitative mono-specific ELISAs.…”

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

“…The interaction between TFF3 and mucins has also been reported to protect intestinal epithelia from injuries, maintaining mucosal barrier function (26). Furthermore, mitogenic effects of TFF3 have been identified in vitro in primary cell culture, and TFF3 has been demonstrated to inhibit apoptosis, induce cellular invasion, act as an inflammatory modulator and exhibit pro-angiogenic activity (27)(28)(29)(30)(31)(32). A protective or healing effect of TFF3 has also been reported in a series of experiments, such as cells in vitro, mice, rats and human (12)(13)(14)(15)(16)(17).…”