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Background: Pancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays a key role in the occurrence and development of PC. The purpose of this study is to analyze trends by year, country, institution, journal, reference and keyword in publications on the PC microenvironment and to predict future research hotspots. Methods: The Web of Science Core Collection was used to search for publications. We analyzed the contributions of various countries/regions, institutes, and authors and identified research hotspots and promising future trends using the CiteSpace and VOSviewer programs. We also summarized relevant completed clinical trials. Results: A total of 2,155 papers on the PC microenvironment published between 2011 and 2021 were included in the study. The number of publications has increased every year. The average number of citations per article was 32.69. The USA had the most publications, followed by China, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed two clusters of keywords: basic research and clinical application. The co-occurrence cluster analysis showed glutamine metabolism, carcinoma-associated fibroblasts, oxidative phosphorylation as the highly concerned research topics of basic research in recently. The three latest hot topics in clinical application are liposomes, endoscopic ultrasound and photodynamic therapy. Conclusion: The number of publications and research interest have generally increased, and the USA has made prominent contributions to the study of the tumor microenvironment of PC. The current research hotspots mainly focus on energy metabolism in the hypoxic tumor microenvironment, cancer associated fibroblasts in regulating the tumor microenvironment, accurate diagnosis, drug delivery and new treatments.
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BACKGROUND: Gastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. The aim of the present study was to screen candidate biomarkers associated with the pathogenesis and prognosis of GC by a novel strategy. METHODS: The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 5% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in three Gene Expression Omnibus (GEO) datasets. Further, a prognostic risk model was constructed by multivariate Cox regression analysis in GEO dataset and validated in The Cancer Genome Atlas (TCGA). The expression level of candidate biomarkers was determined in serum and serum-derived exosomes of GC patients. Moreover, the effect of biomarkers in exosomes on migration of GC cells was analyzed by transwell assay. RESULTS: Ten candidate biomarkers (AGT, SERPINH1, WNT2, LIPG, PLAU, COL1A1, MMP7, MXRA5, CXCL1 and COL11A1) were identified with efficient diagnostic value in GC. A prognostic gene signature consisted of AGT, SERPINH1 and MMP7 was constructed and showed a good performance in predicting overall survivals in TCGA. Consistently, serum levels of the three biomarkers also showed high sensitivity and specificity in distinguishing GC patients from controls. In addition, the expression level of the three biomarkers were associated with malignant degree and decreased after surgery in GC patients. Moreover, the expression level of AGT and MMP7 in exosomes correlated positively with serum level. The exosomes derived from serum of GC patients can promote migration of SGC-7901 cells. After neutralized the expression level of three proteins in exosomes with antibodies, the migration of GC cells was obviously suppressed. CONCLUSIONS: Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that the three-gene signature was a candidate diagnostic and prognostic biomarker for patients with GC.
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OBJECTIVE: To investigate the effect of exosomes derived from colon cancer (CC) cells and plasma of CC patients on migration of SW480 cells. METHODS: The exosomes derived from culture medium of human colon epithelial cell line NCM460 and CC cell line SW620 were isolated by ultracentrifugation. The exosomes derived from plasma of CC patients and healthy controls were isolated by size exclusion chromatography (SEC). The particle size and morphology of exosomes were identified by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) respectively, and exosomal markers were detected by Western blotting. The uptake of fluorescent DiI labeled exosomes by SW480 cells was observed by confocal microscopy. Transwell assay was used to detect the effect of exosomes on the migration of SW480 cells. The expression level of associated proteins in signaling pathway were analyzed by Western blotting. Rapamycin, an inhibitor of mTOR, was used to study the role of mTOR signaling pathway on exosomes mediated migration of SW480 cells. RESULTS: The results of NTA and TEM showed that the particle size of the isolated exosomes was about 120 nm, which were small vesicles with membrane structure. The expressions of exosomal markers Alix, TSG101 and CD63 could be detected. The exosomes were evidenced by a red fluorescent signal inside the cytoplasm of SW480 recipient cells, and could promote the migration of SW480 cells, which is associated with Akt/mTOR signaling pathway. Compared with the control group, plasma exosomes derived from CC patients could significantly promote the migration of SW480 cells. Inhibition the activity of mTOR signaling could attenuate the migration of SW480 cells. CONCLUSIONS: Exosomes derived from CC cells and plasma of CC patients could promote the migration of SW480 cells, which is associated with Akt/mTOR signaling pathway.
