Lung cancer is the most common and fatal malignant tumor in the world. The tumor microenvironment (TME) is closely related to the occurrence and development of lung cancer, in which the inflammatory microenvironment plays an important role. Inflammatory cells and inflammatory factors in the tumor inflammatory microenvironment promote the activation of the NF-κB and STAT3 inflammatory pathways and the occurrence, development, and metastasis of lung cancer by promoting immune escape, tumor angiogenesis, epithelial–mesenchymal transition, apoptosis, and other mechanisms. Clinical and epidemiological studies have also shown a strong relationship among chronic infection, inflammation, inflammatory microenvironment, and lung cancer. The relationship between inflammation and lung cancer can be better understood through the gradual understanding of the tumor inflammatory microenvironment, which is advantageous to find more therapeutic targets for lung cancer.
Background Non‐small cell lung cancer (NSCLC) is one of the leading causes of cancer‐related death globally. This study aimed to disclose the role of circular RNA circ_0072088 in NSCLC and illustrate its potential mechanism. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was applied to detect the expression of circ_0072088, zinc finger RNA binding protein (ZFR), microRNA‐377‐5p (miR‐377‐5p) and NOVA alternative splicing regulator 2 (NOVA2). The viability, colony formation, cell cycle, migration and invasion of NSCLC cells were measured by cell counting kit‐8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell invasion assay. Western blot assay was employed to examine the protein levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metallopeptidase 2 (MMP2), MMP9 and NOVA2. The downstream targets of circ_0072088 and miR‐377‐5p were searched through using circular RNA Interactome and TargetScan databases, and the interaction between miR‐377‐5p and circ_0072088 or NOVA2 was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. in vivo tumor growth assay was used to evaluate the functions of circ_0072088 in the progression of NSCLC in vivo. Results GSE101586 dataset and the analysis of tissue specimens showed that circ_0072088 was aberrantly upregulated in tumor tissues of lung cancer and NSCLC. Circ_0072088 interference caused marked suppression on the proliferation and motility of NSCLC cells. Circ_0072088 could negatively regulate miR‐377‐5p through direct combination. Circ_0072088 contributed to the progression of NSCLC through sponging miR‐377‐5p. MiR‐377‐5p could directly interact with NOVA2, and the overexpression of NOVA2 overturned miR‐377‐5p‐mediated influence on NSCLC cells. Circ_0072088 facilitated the progression of NSCLC in vivo. Conclusions Circ_0072088 facilitated the proliferation and metastasis of NSCLC cells through upregulating NOVA2 via functioning as a competitive endogenous RNA (ceRNA) for miR‐377‐5p.
Background. The prognosis of non-small-cell lung cancer (NSCLC) has not been significantly improved. In the past several years, research on epigenetics is in full swing. There is a focus on the gene EZH2; however, its role as a predictor of the prognosis of NSCLC is in the debate. Objective. To clarify if the expression level of EZH2 can influence the prognosis of NSCLC and explain its prognostic value. Methods. We have systematically searched PubMed, Web of Science, and Cochrane library, screened relevant articles, and conducted a meta-analysis on the expression level of EZH2 in NSCLC. We collected the hazard ratio (HR) and the 95% confidence interval (CI) and used STATA 12.0 to calculate the combined result of EZH2 overall survival. In addition, we conducted subgroup analyses, a sensitivity analysis, and a funnel plot to test the reliability of the results. We further validated these meta-analysis results using the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) database. In addition, we have investigated the correlation between EZH2 expression and EGFR expression, KRAS expression, BRAF expression, and smoking in TCGA database to further explore the mechanism behind the influence of high EZH2 expression on lung cancer prognosis. Results. 13 studies including 2180 participants were included in the meta-analysis. We found that high expression of EZH2 indicates a poor prognosis of NSCLC ( HR = 1.65 and 95% CI 1.16-2.35; p ≤ 0.001 ). Subgroup analyses showed high heterogeneity in stages I-IV ( I 2 = 85.1 % and p ≤ 0.001 ) and stages I-III ( I 2 = 66.9 % and p = 0.029 ) but not in stage I ( I 2 = 0.00 % and p = 0.589 ). In the Kaplan-Meier plotter database, there was a high expression in 963 cases and low expression in 964 cases ( HR = 1.31 and 95% CI 1.15-1.48; p < 0.05 ). Further analysis found that the high expression of EZH2 was statistically significant in lung adenocarcinoma ( HR = 1.27 and 95% CI 1.01−1.6; p = 0.045 ), but not in lung squamous cell carcinoma ( HR = 1.03 and 95% CI 0.81−1.3; p = 0.820 ). The results of the TCGA database showed that the expression of EZH2 in normal tissues was lower than that in lung cancer tissues ( p < 0.05 ). Smoking was associated with high expression of EZH2 ( p < 0.001 ). EZH2 was also highly expressed in lung cancers with positive KRAS expression, and the correlation was positive in lung adenocarcinoma ( r = 0.3129 and p < 0.001 ). The correlation was also positive in lung squamous cell carcinoma ( r = 0.3567 and p < 0.001 ). EZH2 expression was positively correlated with BRAF expression ( r = 0.2397 and p < 0.001 ), especially in lung squamous cell carcinoma ( r = 0.3662 and p < 0.001 ). In lung squamous cell carcinoma, a positive yet weak correlation was observed between EZH2 expression and EGFR expression ( r = 0.1122 and p < 0.001 ). Conclusions. The high expression of EZH2 indicates a poor prognosis of NSCLC, which may be related to tumor stage or cancer type. EZH2 may be an independent prognostic factor for NSCLC. EZH2 high expression or its synergistic action with KRAS and BRAF mutations affects the prognosis of non-small-cell lung cancer.
Background: There are no useful biomarkers for the clinical outcome of advanced esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the prognostic value of soluble PD-L1 (sPD-L1) in serum of patients with locally advanced or metastatic ESCC who received cytotoxic chemotherapy as first-line treatment. Materials and Methods: This study evaluated the expression pattern of PD-L1 by immunohistochemistry and sPD-L1 concentration, and correlation with clinicopathological factors and overall survival (OS) in 190 patients with ESCC. Results: sPD-L1 concentration was highly expressed in ESCC, especially in female patients. Patients with a high sPD-L1 level (≥0.63 ng/mL) had a shorter OS than those with a low sPD-L1 level (<0.63 ng/mL). In a multivariate analysis, high sPD-L1 concentration remained an independent prognostic factor of OS after adjustment for possible confounders. However, tissue PD-L1 expression level was non-prognostic in this study. Conclusion:There was no significant correlation between serum sPD-L1 concentration and tissue PD-L1 expression level. sPD-L1 concentration before treatment could be an effective and convenient biomarker of prognosis in patients with locally advanced or metastatic ESCC treated with combination cytotoxic chemotherapy.
Background: Nonalcoholic fatty liver disease is a common reason for chronic liver disease in children and adults. The increasing incidence of the disease has become one of the most critical public health problems in the 21st century, closely related to genetic and environmental factors. So far, apart from changing lifestyle and diet, modern medicine still lacks effective treatment measures. Chinese patent medicine has the advantages of apparent curative effect, overall regulation and fewer side effects. However, there is a lack of research on the simultaneous comparison of various Chinese patent medicines. Therefore, we used a reticular meta-analysis to indirectly compare the efficacy and safety of different oral Chinese patent medicines through standard reference. Method: We will conduct a comprehensive and systematic search of Chinese and English databases from the beginning to December 2020. All randomized controlled trials (RCTs) of oral Chinese patent medicine for NAFLD in children will be searched. The 2 researchers then independently filter the retrieved literature, extract the data according to the data extraction table and assess the risk of bias. We will perform a pair of meta-analyses and a Bayesian network meta-analysis. STATA and Win BUGS software will be used for data analysis. Results: This study will thoroughly compare and analyze the differences in the efficacy of all kinds of TCPM in NAFLD treatment in childhood or adolescence. Conclusion: This study will provide reference and evidence support for clinical drug selection optimization. Ethics and dissemination: This study does not require ethical approval. INPLASY registration number: 2020120068.
Randomized controlled trials regarding efficacy and safety of TCM in the treatment of TNBC. I: TCM or TCM combined with other treatments (including surgery, radiotherapy, chemotherapy, Chinese medicine, etc.).
Sun et al. Efficacy and safety of Yangzheng xiaoji capsule combined with TACE for intermediate and advanced hepatocellular carcinoma:A protocol for systematic review and meta-analysis. Inplasy protocol 2021100066.
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