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.
MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.
PurposeThe purpose of this research is to investigate the prognostic factors of patients with stage I gastric cancer (GC) and to determine whether adjuvant chemotherapy improves the prognosis for high-risk patients.MethodsWe performed a retrospective analysis at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences from January 2001 to December 2015. Cox regression and Kaplan-Meier were used to evaluate the relationship between the patients’ clinicopathologic characteristics and prognosis.ResultsA total of 1,550 patients were eligible for the study. The 5-year disease-free survival (DFS) rate of all enrolled patients was 96.5%. The pT and pN stages were significantly associated with the prognosis. The 5-year DFS rates of the three subgroups (T1N0, T2N0, and T1N1) were 97.8%, 95.7%, and 90.5%, respectively (p < 0.001). In the T1N1 subgroup, patients not undergoing chemotherapy showed a lower 5-year DFS rate compared to those undergoing chemotherapy, although the difference was not statistically significant.ConclusionsBoth the pT and pN stages were closely associated with the prognosis of patients with stage I GC. We also found that the danger coefficient of the pN stage was higher than that of the pT stage, and that postoperative adjuvant chemotherapy might be a reasonable approach to improve outcomes of high-risk patients, particularly in the T1N1 group.
The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2-positive NCI-N87 cell lines (Tzb-refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb-refractory cells. The viability of parental NCI-N87 and Tzb-refractory cells with an autophagy inhibitor or inducer was also examined. The results of the present study indicated that autophagic flux may have an important function in the resistance of HER2-positive human gastric cancer NCI-N87 cells to Tzb. Tzb resistance in NCI-N87 cells prevents cell apoptosis via autophagic flux inhibition. Tzb may activate the Akt/mTOR pathway to inhibit autophagic flux in gastric cancer cell lines. Everolimus, an mTOR inhibitor, may inhibit cell viability, indicating that the mTOR pathway may serve a function in HER2-positive gastric cancer and that the resistance of HER2-positive gastric cancer to Tzb may, at least partially, be due to activation of the mTOR pathway.
<b><i>Background:</i></b> The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). <b><i>Results:</i></b> A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients’ OS (HR, 0.49; 95% CI: 0.37–0.61) and PFS (HR, 0.52; 95% CI: 0.36–0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27–0.88) and DFS (HR, 0.49; 95% CI: 0.31–0.68). <b><i>Conclusion:</i></b> HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.
Background and objective: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. Methods:A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. Results:The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC).Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR <154. Conclusions:Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.
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