BackgroundThe tumor microenvironment represents an abnormal niche containing numerous factors, such as T cells, dendritic cells (DCs), regulatory T cells (Tregs), and indoleamine 2,3‐dioxygenase (IDO), involved in maintaining immune homeostasis and tolerance. All these factors may influence the choice of therapy and the clinical outcomes.MethodsFlow cytometry was performed to identify CD4+/CD8 + T cells and DCs, and immunohistochemistry was used to evaluate IDO and Forkhead Box P3 (Foxp3) expression; these experiments were performed in order to explore the clinical and prognostic significance of CD4/CD8 + T cells, DCs, Tregs, and IDO expression in gastric carcinoma.ResultsSmaller tumor size was correlated with higher expression levels of peripheral CD4 + T cells (P = .003) and CD8 + T cells (P = .002), and lower IDO expression (P = .044) in tumors. Well‐differentiated gastric carcinomas displayed higher peripheral (P = .029) and tumor‐infiltrating CD4 + T cell (P = .009) populations and a higher tumor‐infiltrating DC1/DC2 ratio (P = .048). Gastric cancer in the early T stages exhibited higher populations of peripheral DC2s (P = .044) and a higher tumor‐infiltrating DC1/DC2 ratio (P = .012). Gastric cancer at the N0 stage had lower tumor‐infiltrating DC2s (P = .032) and a higher DC1/DC2 ratio (P = .037). IDO expression was positively correlated with tumor‐infiltrating Foxp3 + Tregs (P < .001) as well as DC2s (P < .001), whereas it was negatively correlated with the tumor‐infiltrating CD4/CD8 + T cell ratio (P = .023). Tumor‐infiltrating Foxp3 + Treg was positively correlated with tumor‐infiltrating DC2s (r 2 = 0.772; P < .001). At T, N, and TNM stages, the expression levels of peripheral DC2s, tumor‐infiltrating DC1/DC2 ratios, Foxp3 + Tregs, and IDO were significantly correlated with prognosis (P < .05). The T stage and peripheral DC2s were significant risk factors for overall survival.ConclusionImmunocompetent cells and humoral immune factors, including DC2s, CD4+/CD8 + T cells, Foxp3 + Tregs, and IDO, interact with each other to compose a complex community of tumor immune microenvironment, ultimately affecting tumor progression and survival of gastric cancer.
The abnormal distributions of memory T cells (Tm) and dendritic cells (DC) in stomach cancer are not well understood. Indoleamine 2,3-dioxygenase (IDO), produced by DC, may be an important enzyme affecting function and proliferation of Tm. In this study, IDO expression was examined by immunohistochemical staining. The subsets of Tm and DC were counted by flow cytometry. The percentages of CD4 + Tm and CD4 + central Tm (Tcm) were lower in tumor tissues than in normal tissues (P < 0.05), while the CD4 + effector Tm (Tem) and CD8 + Tem percentages were higher in tumor tissues (P < 0.05). The ratio of myeloid DC (DC1)/plasmacytoid DC (DC2) was significantly lower in tumor tissues (P = 0.009). The high expression of IDO was more frequently observed in tumor tissues (P = 0.001). The percentages of CD4 + Tm and CD8 + Tm were positively associated with DC1 percentage and ratio of DC1/DC2 (P < 0.05). The higher CD8 + Tcm percentage was associated with higher DC2 percentage (P = 0.025). The patients with high IDO expression had significantly lower CD4 + Tm (P = 0.012) and CD8 + Tm percentages (P = 0.033), but higher CD8 + Tem percentage (P < 0.01). Concerning on clinicopathologic features, the higher DC2 percentage was associated with larger tumor size (P = 0.019). The CD4 + Tm and CD8 + Tem percentages were significantly associated with clinical stage and lymph node metastasis; the high IDO expressions were significantly associated with deeper tumor invasion (P = 0.016) and lymph node metastasis (P = 0.038). Thus, DC subsets, Tm subsets, and IDO expression were correlated with each other. They were associated with the established clinicopathologic features, such as tumor size, depth of invasion, lymph node metastasis, and clinical stage.
Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients.
Background miRNA 106b~25 cluster were demonstrated to be an oncogene. In previous study, we had analyzed the diagnostic significance of miRNA 106b~25 based on its carcinogenesis effect. The significance of miRNA 106b~25 for prognosis of gastric cancer were not researched. Methods We applied multivariate analysis of PCA, PLS-DA and Cox Regression for clinicopathological features and survival time to explore the significance of miRNA 106b~25 expression in plasma and cancer tissues for gastric cancer. Results The expression of miRNA 106b, miRNA 93 and miRNA 25 in plasma were positively correlated with their expression in tumor tissues. Via PCA analysis, it was found that miRNA 106b~25 expression in plasma and tumor, T, N and TNM stage were correlated with each other. Via PLS-DA analysis, we identified that T, N and TNM stage were important factors for miRNA 106b~25 expression both in plasma and tumor (all VIP value > 1.2). According to loading weights of variables for the first and second components, it was found that the importance of the miRNA 106b~25s expression carried with the progressed stage of gastric cancer. In the survival analysis, COX regression showed that T stage, plasma miRNA 106b and tumor miRNA 93 were significant risk factors for overall survival [HR: 0.400 (0.205–0.780); P = 0.007; HR: 0.371 (0.142–0.969), P = 0.043; 0.295 (0.134–0.650), P = 0.002]. Conclusion Plasma and tumor miRNA 106b~25 expression correlated with T, N and TNM stage. Increased miRNA 106b~25 expression was important characters carried with gastric cancer progression. T stage, plasma miRNA106b and tumor miRNA 93 significant risk factors for overall survival. Electronic supplementary material The online version of this article (10.1186/s12935-019-0918-7) contains supplementary material, which is available to authorized users.
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