6997

TDGF1

teratocarcinoma-derived growth factor 1;TDGF1;teratocarcinoma-derived growth factor 1

cripto-1 growth factor|epidermal growth factor-like cripto protein CR1

3p21.31

protein-coding

Teratocarcinoma-derived growth factor 1 (TDGF1) is a member of the epidermal growth factor-cripto FRL1 cryptic protein family and is involved in the activation of several different signaling pathways during embryonic development and cellular transformation. Previous reports show that TDGF1 regulates the activation of several signaling pathways and controls cellular transformation in embryonic status, whereas its significance in colorectal cancer (CRC) is not yet fully understood. The present study comprised 55 patients who underwent surgery for CRC, as well as two cell lines derived from human CRC. The correlation of gene expression with clinical parameters in patients was assessed. The biological significance of TDGF1 expression was evaluated by knockdown experiments in the cell lines. Seventeen of 55 (30.9%) cases exhibited a higher TDGF1 expression in cancerous regions than in marginal non-cancerous regions. Patients with high TDGF1 expression were statistically susceptible to a recurrence of the disease, and showed poorer disease-free survival than those with low expression. The assessment of TDGF1 knock-down in the 2 cell lines demonstrated that the siRNA inhibition resulted in a statistically significant reduction in cell growth and invasion. In conclusion, the present data strongly suggest the usefulness of TDGF1 as a predictive marker for metachronous metastasis in CRC patients.

AIMS: Cripto-1 may be capable of up-regulating signalling molecules associated with epithelial-to-mesenchymal transition (EMT), an important event characterized by loss of E-cadherin during malignant tumour progression and metastasis. The aim was to investigate the expression of Cripto-1 and E-cadherin in relation to clinicopathological features and patient prognosis of gastric cancer. METHODS AND RESULTS: The expression of Cripto-1 and E-cadherin was studied by immunohistochemistry in 118 gastric cancer cases. Up-regulated Cripto-1 (CR+) was found in 54% (64/118) of cases, whereas down-regulated E-cadherin (E-cad-) was found in 70% (83/118) of cases. Either CR+ or E-cad- was associated with lymph node metastasis, liver metastasis and late TNM stage (P < 0.05). Patients with either CR- or E-cad+ showed higher 5-year survival rates than those with CR+ or E-cad- (P = 0.0012 and P = 0.0017, respectively). When combined, evaluation of these two proteins, simultaneous CR+ and E-cad- (CR+/E-cad-) in cancer was strongly associated with the above three aggressive clinicopathological features (P < 0.001) and indicated the worst patient survival (P = 0.0001). Multivariate analysis revealed that CR+/E-cad- was an independent prognostic factor in gastric cancer. CONCLUSIONS: Combined analysis of Cripto-1 and E-cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis.

AIM: To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis. METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal metaplasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were significantly higher in GC with lymph node metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relationship between CR-1 and p-STAT3 expressions in GC (r(k) = 0.189, P = 0.002). CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.