Long noncoding RNAs (lncRNAs) have been shown to regulate tumor biology and might be used for cancer diagnosis, prognosis and potential therapeutic targets. Although up-regulation of lncRNA UCA1 (urothelial carcinoma-associated 1) in several cancers has been found, its role in gastric cancer remains elusive. The aim of this study was to detect the expression of lncRNA UCA1 in gastric cancer and its clinical association. The expression of UCA1 was detected in 112 pairs of tumorous and adjacent normal tissues from patients with gastric cancer, as well as in four gastric cancer cell lines and a human normal gastric epithelium cell line using RT-qPCR. Results showed that UCA1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control. Clinicopathologic analysis revealed that high UCA1 expression correlated with worse differentiation, tumor size, invasion depth and TNM stage in gastric cancer. Kaplan-Meier analysis showed that increased UCA1 expression contributed to poor overall survival (p = 0.017) and disease-free survival (p = 0.024) of patients. A multivariate survival analysis also indicated that UCA1 could be an independent prognostic marker. The levels of UCA1 in gastric juice from gastric patients were significantly higher than those from normal subjects (p = 0.016). Moreover, validation analysis showed that UCA1 levels were robust in differentiating gastric cancer patients from control subjects [area under the curve (AUC) = 0.721; 95 % confidence interval (CI) = 0.655-0.788, p < 0.01]. These results suggested that UCA1 might serve as a promising biomarker for early detection and prognosis prediction of gastric cancer.
This study was designed to investigate the distribution of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients, its clinical significance, and the expression profile of Th17 cell-associated cytokines. The percentage of Th17 cells detected by flow cytometry analysis (FACS) was significantly higher in 46 pancreatic tumor tissues (5.28 ± 1.65%) compared with corresponding adjacent normal tissues (2.57 ± 0.83%) (P = 0.031). In addition, the percentage of Th17 cells was significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.039). The percentage of Th17 cells in peripheral blood of 20 pancreatic cancer patients (3.99 ± 1.15%) was significantly higher than 15 healthy volunteers (1.98 ± 0.57%) (P = 0.027). Immunohistochemistry (IHC) was performed to detect IL-17+ cells in 46 pancreatic tumor tissues, as well as expression of CD34 in 24 tumor tissues. IL-17 was shown to mainly locate in cytoplasm, and the frequency of IL-17+ cells in tumor tissues (39/46) was higher than control (29/46). The presence of IL-17+ cells in tumor tissues was associated with tumor, node, and metastasis (TNM) stage, and lymph node metastasis (P = 0.012 and P = 0.009) but not with patient sex, age, tumor size, and histological grade (P > 0.05). Interestingly, distribution of Th17 cells in tumor tissues was positively correlated with microvessel density (MVD) (r = 0.86, P = 0.018). Furthermore, the median survival time of patients with high and low level of IL-17+ cells frequency was 14.5 and 18.5 months respectively (P = 0.023). The serum levels of Th17 cell-associated cytokines, IL-17 and IL-23 in 20 pancreatic patients detected by enzyme-linked immunosorbent assay (ELISA) were 69.2 ± 28.5 pg/mL and 266.5 ± 98.1 pg/mL, respectively, which were significantly higher than 15 healthy volunteers (P = 0.015 and P = 0.02). Moreover, levels of IL-17 and IL-23 were significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.04 and P = 0.036). This study suggests that increase in Th17 cells frequency and its related cytokines levels in pancreatic tumor tissues may indicate involvement in the invasion and metastasis of pancreatic cancer, which may thereby affect patient prognosis. Therefore, Th17 cells and related cytokines may be served as important immune indicators for predicting the prognosis of pancreatic cancer patients.
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