3(0 6-429 9) 0 001

13 0(0 6-69 1) 0 961    poorly 26 113

3(0.6-429.9) 0.001

13.0(0.6-69.1) 0.961    poorly 26 113.1(1.6-530.3)   11.9(1.2-37.9)   *p by the Mann-Whitney U test AMN-107 Table 3 Logistic regression analysis of the association between tumor stage and clinicopathological features (n = 63)   B SEM Chi-squared p-value OR (95% CI) Sex 0.241 1.110 0.037 0.847 1.239(0.141-10.922) Age -0.063 0.040 2.484 0.115 0.939(0.868-1.015) Tobacco use 1.173 1.102 1.133 0.287 3.231(0.373-28.005) Histology 0.292 0.531 0.303 0.582 1.339(0.473-3.793) High level IL-10 expression in TAM 2.952 0.742 15.844 0.0001 19.137(4.474-81.859) The dependent variable is early- or late-stage group The independent variables included sex (0 = female; 1 = male), age (continuous variable, in yrs), Tobacco use (0 = Current,1 = Former,2 = Never), histology (1 = adenocarcinoma; 2 = squamous cell carcinoma;3 = others) and IL-10 expression (0 = low (<30.5); 1 = high (≥30.5). OR: odds ratio; CI: confidence interval. The increased mRNA expression of IL-10 was also associated with lymph node metastasis, lymphovascular invasion, pleural invasion and poor differentiation (p < 0.0001, p = 0.010, p = 0.017 p = 0.001, respectively). A correlation between cathepsin B mRNA expression in TAM with NSCLC tumor T status was found (p = 0.037). Otherwise, there was no significant relationship between the

mRNA expression of cathepsin B with any other clinicopathological factors (all p > 0.05). Discussion Increased infiltration Emricasan of TAMs into NSCLC correlates with a poor prognosis [5, 9]. However, the mechanisms for this effect remain unclear. TAM derived molecules that function to suppress immune activation, LY3023414 promote extracellular

matrix (ECM) remodeling may play important roles in NSCLC progression. In the present study, the rational we selected IL-10, cathepsin B or cathepsin S, is that they were reported to be closely associated with TAMs in recent literatures [10–12, 24]. IL-10 is widely known as an potent immunosuppressive cytokine associated with cancer [13, 25]. It is produced by a number of cells, including tumor cells Glycogen branching enzyme and TAMs[14, 25]. Cathepsins B, cathepsin S, proteolytic enzymes, were thought to facilitate the breakdown of basement membranes thereby promoting cancer cell invasion into surrounding normal tissues. TAM expressed cathepsin B or cathepsin S in pancreatic islet, breast or prostate cancer animal models. In our study, we showed, TAM expressed high levels of IL-10, cathepsin B, but not cathepsin S in NSCLC. Our study suggested that increased IL-10 expression of TAM in NSCLC patients correlated with late stage disease (stage II, III and IV), lymph node metastases, pleural invasion, lymphovascular invasion and poor differentiation.

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