Objective To investigate the correlations of calmodulin 1 (CNN1) and asymmetric dimethylarginine (ADMA) expression with Wnt/β-catenin pathway in tissues of gastric cancer and their values for prognosis.

Methods Surgical specimens and serum samples from 110 patients with gastric cancer, along with serum samples from 60 healthy individuals in the hospital were collected. Immunohistochemistry and real-time fluorescent quantitative PCR were used to detect the expression levels of CNN1 protein and CNN1 mRNA in gastric cancer tissues respectively; the enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of ADMA in the serum of gastric cancer patients. The relationships of the CNN1 and ADMA expression with the clinicopathological characteristics in gastric cancer patients were analyzed. Kaplan-Meier survival curve was used to analyze the influence of CNN1 and ADMA expression on prognosis of gastric cancer patients; Cox regression analysis was used to explore independent factors affecting the prognosis of gastric cancer patients; the Pearson correlation analysis was used to explore the correlation between CNN1 and ADMA expression in gastric cancer tissues, and to analyze the correlations of CNN1 mRNA and ADMA mRNA with Wnt/β-catenin signaling pathway-related indicators.

Results The positive expression rate of CNN1 protein in gastric cancer tissues was 38.18% (42/110), which was significantly lower than 57.27% (63/110) in adjacent tissues (χ²=8.035, P=0.005). The serum ADMA level in gastric cancer patients was (0.54±0.17) μmol/L, which was significantly higher than (0.42±0.14) μmol/L in healthy individuals (t=4.752, P < 0.001). Patients with lymph node metastasis and advanced tumor stages had significantly decreased CNN1 protein positivity in gastric cancer tissues and increased serum ADMA expression (P < 0.05). The survival rate was 73.80% in the high CNN1 expression group (n=42), which was significantly higher than 39.71% in the low CNN1 expression group (n=68) (χ²=22.300, P < 0.001); the survival rate was 45.68% in the high ADMA expression group (n=81), which was significantly lower than 72.41% in the low ADMA expression group (n=29) (χ²=4.791, P=0.029). Univariate and multivariate Cox regression analysis showed that lymph node metastasis, advanced tumor staging, low CNN1 protein expression, and high serum ADMA expression were independent risk factors for poor prognosis in gastric cancer patients (P < 0.05). The expression level of CNN1 mRNA in gastric cancer tissues was (0.41±0.13), which was significantly lower than (1.16±0.35) in adjacent tissues (t=21.068, P < 0.001). The expression levels of wnt3a mRNA and β-catenin mRNA in gastric cancer tissues were (2.02±0.42) and (2.59±0.58) respectively, both were significantly higher than (1.25±0.28) and (1.18±0.42) in adjacent tissues (t=15.999, P < 0.001; t=20.651, P < 0.001). CNN1 expression in gastric cancer tissues was negatively correlated with serum ADMA expression in gastric cancer patients (r=-0.794, P < 0.001); CNN1 mRNA expression in gastric cancer tissues was negatively correlated with the expression of Wnt/β-catenin signaling pathway-related indicators wnt3a mRNA and β-catenin mRNA (P < 0.001); serum ADMA mRNA expression in gastric cancer patients was positively correlated with the expression of Wnt/β-catenin signaling pathway-related indicators wnt3a mRNA and β-catenin mRNA (r=0.763, P < 0.001; r=0.874, P < 0.001).

Conclusion The decreased expression of CNN1 and the increased expression of serum ADMA are independent risk factors for poor prognosis in gastric cancer patients, and their expression levels are related to lymph node metastasis and tumor TNM staging. The expression levels of CNN1 and ADMA are negatively correlated in gastric cancer tissues, which may be mediated by regulating the Wnt/β-catenin signaling pathway.