ABSTRACT
Objective: To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma. Methods: The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University. Results: DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes (log(2)FC>1.2 and FDR<0.01) and 43 down-regulated genes (log(2)FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients (P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues (P<0.05). Conclusions: The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.
Subject(s)
Adenocarcinoma , Stomach Neoplasms , Adenocarcinoma/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Prognosis , Stomach Neoplasms/geneticsABSTRACT
OBJECTIVE: To investigate the expression and significance of FoxM1 in esophageal squamous cell carcinoma (ESCC) cell lines and tissues. METHODS: Western blot assay was used to detect the expression of FoxM1 in human esophageal epithelial cells and esophageal squamous cell cancer cell lines TE1, TE10, TE11 and Eca109 cells. To determine whether down-regulation of FoxM1 expression could inhibit the aggressive phenotype of ESCC cells, we knocked down the expression of FoxM1 by using FoxM1-shRNA in TE1 cells. Then we detected the cell proliferation, migration and invasion of TE1 cells by MTT assay, scratch assay and transwell assay. Furthermore, the effect of FoxM1 knockdown on tumorigenicity in nude mice was evaluated. Finally, immunohistochemical staining was used to detect the expression of FoxM1 in 99 cases of ESCC tissues and adjacent normal esophageal tissues. χ(2) test was used to analyze the correlations between the expression of FoxM1 and clinicopathologic characteristics and prognosis of ESCC patients. RESULTS: Western blot data showed that FoxM1 expression was lower in normal esophageal epithelial cells and highly expressed in four esophageal cancer cell lines, especially in TE1 cells. Knockdown of FoxM1 inhibited the growth, invasion and migration of TE1 cells and reduced their tumorigenicity in nude mice.The positive expression rate of FoxM1 in ESCC was 61.6% (61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05). The positive expression rate of FoxM1 in ESCC tissues was 61.6% (61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05). FoxM1 expression was significantly and positively correlated with lymph node metastasis, clinical stage and invasive depth (P<0.05). The median survival time was 42.3 months in 38 cases of patients with negative FoxM1 expression, and 33.0 months in 61 cases of positive FoxM1 expression, and the difference was statistically significant (P=0.036). CONCLUSIONS: FoxM1 is highly expressed in ESCC, and significantly correlated with the initiation, development and prognosis of esophageal cancer. FOXM1 might be an indicator to predict the prognosis and serve as a potential target for therapy in esophageal cancer.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Forkhead Box Protein M1/metabolism , Animals , Blotting, Western , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Epithelial Cells/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Esophagus/metabolism , Esophagus/pathology , Forkhead Box Protein M1/genetics , Gene Knockdown Techniques , Humans , In Vitro Techniques , Lymphatic Metastasis , Mice , Mice, Nude , Neoplasm Invasiveness , Prognosis , RNA, Small Interfering , Survival AnalysisABSTRACT
Two new compounds, decuroside VI (1) and decursidate (2), were isolated from the roots of Peucedanum decursivum. Their structures were elucidated as 6'-O-crotonyl-nodakenin and 2-[4'-hydroxyphenyl]-glycol mono trans-ferulate on the basis of spectral analyses and chemical methods.
Subject(s)
Glucosides/isolation & purification , Phenols/isolation & purification , Plants, Medicinal/chemistry , Chromatography, High Pressure Liquid , Coumarins , Glucosides/chemistry , Magnetic Resonance Spectroscopy , Medicine, Chinese Traditional , Molecular Structure , Phenols/chemistry , Plant Roots/chemistry , Spectrophotometry, Infrared , Stereoisomerism , Structure-Activity RelationshipABSTRACT
AIM: To study the chemical constituents of Peucedanum decursivum. METHODS: Various column chromatographies with silica gel and HPLC were employed for the isolation and purification. The structures of the compounds were elucidated on basis of spectral analyses and chemical methods. RESULTS: Seven compounds were isolated from the roots of Peucedanum decursivum (Miq.) Maxim. 1 is 3'(S)-hydroxy-4' (R)-angeloyloxy-3',4'-dihydroxanthyletin, named Decursitin D; 2 is 3'(S)-acetoxy-4'(R)-hydroxy-3',4'-dihydroxanthyletin, named decurstin F; the others are 3'(S)-acetoxy-4'(R)-angeloyloxy-3', 4'-dihydroxanthyletin (3), Pd-C-IV (4), Pd-C-II (5), (+)-3'S-decursinol (6) and (+)-trans-decursidinol (7). CONCLUSION: Compounds 1 and 2 are new compounds, while compounds 6 and 7 were isolated from Peucedanum decursivum (Miq.) Maxim for the first time.
Subject(s)
Apiaceae/chemistry , Coumarins/isolation & purification , Plants, Medicinal/chemistry , Coumarins/chemistry , Molecular Structure , Plant Roots/chemistryABSTRACT
A new ent-kaurane diterpenoid dimer, fritillebinide C(1) together with one known diterpenoid dimer fritillebinide B (2) were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu et G.Q. Ji. Compound 1 has been determined to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(S)-aldehyde(1) by means of spectral analysis and chemical evidence.
Subject(s)
Diterpenes/chemistry , Liliaceae/chemistry , Chromatography , Dimerization , Diterpenes/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Structures/chemistryABSTRACT
A novel ent-kaurane diterpenoid dimer, fritillebinide B (1) together with one known diterpenoid dimer fritillebinide A (2) were isolated from the bulbs of Fritillaria eheiensis var. purpurea G.D. Yu et P. Li. Compound 1 has been established to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(R)-aldehyde (1) by means of spectral analysis and chemical evidence.
