Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
ObjectiveTo observe the effects of overexpression of S100A4 protein on retinal capillary cells and retinal ganglion cells (RGC) after retinal ischemia-reperfusion injury (RIRI). MethodsOne hundred healthy adult male C57BL/6 mice were randomly divided into normal control group (group C), RIRI group, adeno-associated virus (AAV2)-S100A4 green fluorescent protein (GFP) intravitreal injection group (group S), RIRI+AAV2-GFP intravitreal injection group (group GIR), and RIRI+AAV2-S100A4-GFP intravitreal injection group (group SIR), with 20 mice in each group. The RIRI model was established using the high intraocular pressure anterior chamber method in the RIRI, GIR and SIR groups of mice. Eyes were enucleated 3 days after modelling by over anaesthesia. The number of retinal capillary endothelial cells and pericytes in the retinal capillaries of mice in each group was observed by retinal trypsinised sections and hematoxylin-eosin and periodic acid-Schiff staining; immunofluorescence staining was used to observe endothelial cell, pericyte coverage and RGC survival; The relative expression of Toll-like receptor 4 (TLR4), p38 MAPK and nuclear factor erythroid 2-related factor 2 (NRF2) in retinal tissues was measured by Western blot. One-way analysis of variance was used to compare data between groups. ResultsThree days after modeling, the endothelial cell to pericyte ratio in group C was compared with group S and SIR, and the difference was not statistically significant (F=106.30, P＞0.05); the SIR group was compared with group RIRI and GIR, and the difference was statistically significant (F=106.30, P＜0.000 1). Comparison of endothelial cell coverage in each group, the difference was not statistically significant (F=3.44, P＞0.05); compared with the pericyte coverage in group C, the RIRI group and the GIR group were significantly lower, and the difference was statistically significant (F=62.69, P＜0.001). Compared with the RGC survival rate in group C, it was significantly lower in RIRI and GIR groups, and the difference was statistically significant (F=171.60, P＜0.000 1); compared with RIRI and GIR groups, the RGC survival rate in SIR group was significantly higher, and the difference was statistically significant (F=171.60, P＜0.000 1). The relative expression levels of TLR4, p38 and NRF2 proteins were statistically significant among all groups (F=42.65, 20.78, 11.55; P＜0.05). ConclusionsPericytes are more sensitive to ischemia than endothelial cells after retinal RIRI in mice, and early vascular cell loss is dominated by pericytes rather than endothelial cells. The overexpression of S100A4 protein protects against loss of pericytes and RGC after RIRI by inhibiting the TLR4/p38/NRF2 signaling pathway.
Objective To study the expressions of Delta-like ligand 4 （DLL4） and S100A4 in breast carcinoma of differect molecular subtypes and explore its clinical significance. Methods The expressions of DLL4 and S100A4 in all molecular subtypes were tested by SP immunohistochemistry in 108 cases of breast carcinoma and 40 cases of paracancerous tissues from Taihe Hospital. The Luminal A， Lumianl B， HER-2 over-expression， and basal-like subtypes was 51， 26， 17， and 14 cases， respectively. Then the correlation of DLL4 and S100A4 expression with patients’ clinical and pathological features were analyzed. Results The positive expression rates of DLL4 and S100A4 in breast carcinoma was 67.6%（73/108）and 62.0%（67/108）respectively， which were significantly higher than those in paracancerous tissues〔22.5%（9/40） and 45.0%（18/40）〕， P＜0.05. The positive expression rates of DLL4 and S100A4 in breast carcinoma tissues of HER-2 over-expression and basal-like subtypes were significantly higher than those in breast carcinoma tissues of Luminal A and Luminal B subtypes （P＜0.05）. The expressions of DLL4 and S100A4 in breast carcinoma tissues with lymph node metastasis and without lymph node metastasis were significantly different（P＜0.05）. There was positiver elationship between the expressions of DLL4 and S100A4 in breast carcinoma tissues（rs=0.217，P＜0.01）. Conclusions DLL4 and S100A4 are highly expressed in breast carcinoma tissues of HER-2 over-expression and basal-like subtypes， and are all related with prognosis of breast carcinoma. These results suggest that they might be important factors in breast carcinogenesis and tumor development， metastasis. These proteins are indicators of metastasis and predictors for prognosis of breast carcinoma.