Objective To study the expressions of Wnt5a, MMP2, and MMP14 in the primary lesions of gastric cancer and the influences on clinicopathologic features. Methods The expressions of Wnt5a, MMP2, and MMP14 in the specimens of 106 patients with gastric cancer and 39 patients from the adjacent normal gastric tissues were detected by immunohistochemical staining, χ2 test and non-parametric test were used to analyze the relationships among them and between them and their influences on the clinicopathologic features. Results Extensive expressions of Wnt5a, MMP2, and MMP14 were demonstrated in the gastric cancer, which were significantly higher than those in the normal gastric tissues respectively (Plt;0.05). Positive expression of Wnt5a was associated with larger tumor diameter, deeper depth of invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, Wnt5a expression was also associated with lymphatic infiltration and vascular infiltration (Plt;0.05). The expressions of MMP2 and MMP14 were associated with lymphatic infiltration, but not with vascular infiltration. Higher expressions of MMP2 and MMP14 were correlated with deeper tumor invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, higher expression of MMP2 possesed greater tumor diameter (Plt;0.05). Spearman rank correlation analysis revealed the positive relation between Wnt5a and MMP2 （rs=0.240, P=0.014）, Wnt5a and MMP14 （rs=0.251, P=0.010）, as well as MMP2 and MMP14 （rs=0.444, P=0.000）. Conclusion Higher expressions of Wnt5a, MMP2, and MMP14 seem to promote invasion and metastasis of gastric cancer, and there are positive relations among their expressions.
ObjectiveTo investigate the role of Wnt5a in the mechanism of radiculopathy and the relation between Wnt5a and tumor necrosis factorα(TNF-α) by observing the change of the expression of Wnt5a in the rat model of chronic compression of dorsal root ganglia (CCD). MethodsA total of 192 adult male Sprague Dawley rats were allocated into 4 groups: shame group (group A, n=48), CCD group (group B, n=48), CCD+sal ine group (group C, n=48), and CCD+etanercept group (group D, n=48). An L-shaped needle (about 3.5 mm in length, 0.6 mm in diameter) was inserted into the L5 intervertebral foramen, and the dorsal root ganglia (DRG) was compressed by the needle to prepare the CCD model in groups B, C, and D, and then normal sal ine (5.5 mg/kg) or etanercept was injected intraperitoneally in groups C and D. The intervertebral foramen was exposed in group A. The mechanical pain threshold of the posterior paw was tested by the von Frey filaments at 1, 3, 5, and 7 days after operation; the expressions of Wnt5a protein and mRNA were detected at 3 and 7 days after operation by immunohistochemical staining and RT-PCR, respectively. ResultsThe mechanical pain threshold of groups B and C was significantly lower than that of groups A and D, and in group D than in group A (P < 0.05), but no significant difference was found between groups B and C (P > 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a at 7 days were significantly more than those at 3 days in groups B, C, and D (P < 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a in groups B and C were significantly more than in groups A and D, and in group D than in group A (P < 0.05), but no significant difference was shown between groups B and C (P > 0.05). ConclusionThe expression of Wnt5a in the DRG is increased after CCD. The expression of Wnt5a in the DRG is decreased after the administration of the inhibitor of TNF-α.
Objective To explore the potential roles and mechanism of Wnt5a and its receptors in the pathogenesis of bronchiectasis. Methods From October 2017 to April 2018, outpatients with bronchiectasis who needed bronchoscopy were recruited in the Department of Respiratory and Critical Care Medicine of West China Hospital of Sichuan University. The control group was patients with pulmonary nodules less than 10 mm in diameter by health inspection. Patients who used antibiotics and/or glucocorticoids within the past 4 weeks or had other airway diseases were excluded. Serum and bronchial mucosa were collected for detection of Wnt5a by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR), respectively. The receptor of Wnt5a, Ror2, and the downstream pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, were measured in the bronchial mucosa by real-time PCR. Results From October 2017 to April 2018, 32 outpatients with bronchiectasis were found but only 17 patients finished this study, and simultaneously 18 patients with pulmonary nodules were chosen as control. The level of serum Wnt5a in patients with bronchiectasis were significantly higher than that in the control group (P<0.05). Correlation analyses showed that serum Wnt5a level was positively correlated with the level of serum C reactive protein (r=0.806, P<0.05), but had no relation with the level of white blood cell count, blood neutrophil percentage, pulmonary function or bronchiectasis severe index. The mRNA levels of Wnt5a and its receptor Ror2 in bronchial mucosa of patients with bronchiectasis were significantly higher than those in the control group (P<0.001). The mRNA levels of IL-1β and IL-6 in bronchial mucosa of patients with bronchiectasis were higher than those in the control group (P<0.05). Conclusion Wnt5a may play crucial roles in the development of bronchiectasis through Wnt5a/Ror2 signaling pathways to regulate the release of pro-inflammatory cytokines including IL-1β and IL-6.
ObjectiveTo investigate the effect of Wnt5a derived from tumor-associated fibroblasts （CAFs） on the migration and invasion of gastric cancer cells. MethodsThe differentially expressed genes Wnt5a between CAFs and normal gastric fibroblasts (NGFs) in gastric cancer tissues and their corresponding normal gastric tissues using the GEO database GSE194261 dataset were screened. Immunohistochemical method was used to detect the expression of Wnt5a protein in tissue samples of clinical gastric cancer patients, and the relationship between Wnt5a protein expression and clinicopathological features of gastric cancer was analyzed. CAFs and NGFs were extracted from fresh surgical specimens of gastric cancer patients, and the expression of Wnt5a in CAFs was detected by real-time fluorescence quantitative-polymerase chain reaction and Western blot experiment. Transwell invasion and migration experiment was used to observe the effects of CAFs, inhibition of Wnt5a expression in CAFs and different concentrations of recombinant Wnt5a protein on the migration and invasion ability of gastric cancer MGC-803 and MKN-28 cell lines in vitro. ResultsThrough the screening of GEO database GSE194261 data set, it was found that Wnt5a was more expressed in CAFs than NGFs (P<0.05). Immunohistochemical results showed that the expression of Wnt5a protein in gastric cancer tissues was significantly stronger than that in normal gastric tissues (P<0.05), and the expression of Wnt5a protein was related to T stage of tumor (χ2=5.035, P<0.05), but not related to gender, age, degree of tumor differentiation, lymph node metastasis, vascular invasion and nerve invasion (P>0.05). Inhibiting Wnt5a derived from CAFs could inhibit the invasion and migration of gastric cancer cells. By stimulating gastric cancer cells with different concentrations of human recombinant Wnt5a protein, it was found that when the concentration of human recombinant Wnt5a protein was greater than 100 ng/mL, the invasion and migration abilities of MGC-803 and MKN-28 gastric cancer cells were significantly increased (P<0.05). ConclusionWnt5a is highly expressed in CAFs derived from the interstitial tissue of gastric cancer, which is related to the invasion depth of gastric cancer and can promote the invasion and migration of gastric cancer cells.