1.Research on the relationship between fructose-1, 6-bisphosphatase and chemosensitivity of ovarian carcinoma
Haoran LI ; Mengjiao LI ; Fei LIU ; Ziliang WANG ; Xi CHENG
China Oncology 2017;27(5):340-344
Background and purpose: Epithelial ovarian carcinoma is the most malignant tumor in female reproductive system because of its resistance to chemotherapy. Fructose-1, 6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis used to catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate and inorganic phosphate, thereby inhibiting the effect of glycolysis in tumor cells. This study aimed to investigate the association between the expression of FBP1 and chemosensitivity. Methods: The expression level of FBP1 in ovarian cancer patients was measured by immunohistochemistry. Results: According to the results of immunohistochemistry in 209 ovarian carcinoma specimens, the percentage of positive FBP1 expression was about 49.3% (103/209). Loss of FBP1 was a negative factor of survival (42.6 months vs 62.1 months, P=0.003). Besides, patients who were sensitive to chemotherapy displayed significantly higher scores of FBP1 expression than patients who were resistant to therapy (P=0.007). Conclusion: The rate-limiting enzyme FBP1 in gluconeogenesis can be used as a biomarker for predicting the chemoresistance and prognosis of ovarian cancer patients.
2.Research on the cytostatic effect of bufalin on cervical carcinoma cells and the related mechanism
Fei LIU ; Haoran LI ; Xi CHENG ; Mengjiao LI ; Ziliang WANG ; Li YANG
China Oncology 2015;(10):780-784
Background and purpose:Cervical cancer remains the second leading cause of death in gynecologic malignancies partially because of resistance to chemotherapy. Bufalin, a component of the traditional Chinese medicine Chansu, has been widely used in cancer treatment in China. This study aimed to investigate the effects of bufalin on inhibiting the proliferation of ME180 and C33A and explore its possible mechanism.Methods:The cytostatic effects of bufalin on ME180 and C33A cells were evaluated by CCK8 assay (cell counting kit-8). Glucose levels in ME180 and C33A cells were measured using glucose assay kit. Then the alterations of GLUT1 (glucose transporter 1) and HK2 (hexokinase 2) gene expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of proto-oncogene C-MYC and HIF1α (hypoxia-inducible factor 1α) were determined by Western blot.Results:According to the results of CCK-8, bufalin can significantly inhibit the proliferation of carcinoma cells ME180 and C33A (P=0.027,P=0.018). Test on glycometabolism indicated that glucose uptake in cells treated with bufalin decreased (P=0.034,P=0.036). Results from real-time PCR showed that the expression of glycometabolism related indicators GLUT1 (P=0.019) and HK2 (P=0.016) levels were signiifcantly down-regulated in bufalin treated group. Western blot showed that the expression of C-MYC and HIF1αin cells with bufalin treatment was down-regulated markedly.Conclusion:Bufalin can inhibit the proliferation of the cervical carcinoma cells ME180 and C33A through inhibition of their glucose metabolism.
3.Impact of multidrug resistance-related protein 3 gene silenced by siRNA on the drug resistance of liver cancer cells
Zheng SU ; Bo LIU ; Jianping LIU ; Huayao ZHANG ; Zejian LYU ; Ziliang CHENG
Chinese Journal of Hepatic Surgery(Electronic Edition) 2014;(3):174-177
Objective To observe the impact of multidrug resistance-related protein (MRP) 3 gene silenced by small interfering RNA (siRNA) on the drug resistance of primary liver cancer cells. Methods The drug resistance cell lines HepG2/Adriamycin(ADM) were developed by exposing parental cells to stepwise increasing concentrations of ADM and then MRP3-siRNAs were transfected in HepG2/ADM cells with lipofectamine 2000 liposomes. Three groups were assigned:HepG2 cell group (control group), HepG2/ADM cell group (resistance group) and MRP3-siRNA transfected HepG2/ADM cell group (interference group). The MRP3 mRNA contents of 3 groups were measured by real-time fluorescent quantitative polymerase chain reaction (PCR). The expression of MRP3 protein was detected by Western blot. The 50%inhibitory concentrations (IC50) of ADM, lfuorouracil (5-FU), vincristine, oxaliplatin were determined by methyl thiazolyl tetrazolium (MTT) and the drug resistance indexes (RI) were calculated. The experimental data of 3 groups were compared by one-way analysis of variance, while pairwise comparisons were conducted using LSD-t or t test. Results The mean of MRP3 mRNA content in resistance group (5.16±0.31) was signiifcantly higher than those in control group (3.08±0.27) and interference group (2.85±0.23) (LSD-t=8.765, 10.363;P<0.05). The MRP3 protein content in resistance group (21 063±274) was signiifcantly higher than those in control group (14 476±217) and interference group (6 660±153) (LSD-t=21.836, 79.578;P<0.05). The RI of ADM, 5-FU,vincristine, oxaliplatin in resistance group were 14.40±0.31, 26.68±0.22, 28.70±0.49, 20.23±0.54, and were 3.55±0.16, 9.60±0.27, 2.11±0.17, 3.15±0.13 respectively in interference group. The RI in interference group were signiifcantly lower than those in resistance group (t=53.873, 84.933, 88.811, 53.258; P<0.05). Conclusions MRP3 gene of liver cancer cells silenced by siRNA can improve the cells' sensitivity to chemotherapy drugs and reverse its chemotherapy drug resistance.
4.Effect of breast tissue marker on MRI evaluation for breast lesions and clinical significance
Haiqing LIU ; Hanchen ZHANG ; Ziliang CHENG ; Weike ZENG ; Chang GONG ; Yue HU ; Zhuo WU
Journal of Chinese Physician 2020;22(3):337-341,346
Objective:This study compares the magnetic resonance imaging (MRI) appearance of two types of breast tissue markers to investigate the appropriate clinical application of the markers.Methods:Breast MRI of 69 patients (78 masses) with breast tissue markers had been placed were analyzed retrospectively from November 2015 to August 2018 in our hospital. The sizes and shapes of breast tissue markers were assessed in axial fat-suppressed T2-weighted images, T1-weighted images and contrast-enhanced T1-weighed images.Results:The length of the coil nickel-free stainless steel markers were greater than ribbon titanium markers, with statistical difference in fat-suppressed T2-weighted images ( P=0.039). In contrast-enhanced T1-weighted images, all coil nickel-free stainless steel markers showed >6 mm diameter and round shape, and ribbon titanium markers showed >6 mm diameter ( n=20) or ≤6 mm diameter ( n=8), and round ( n=20), dot ( n=7) or band ( n=1) shapes. The categories of sizes and shapes in two types of breast tissue markers both had statistical significance ( P<0.001, P<0.001). Conclusions:Small breast lesions with breast tissue markers are not suitable for MRI evaluation. The artifact of ribbon titanium markers is smaller than coil nickel-free stainless steel markers, so they have less impact for lesions. The choice of the breast tissue markers and image evaluation methods should depend on the different clinical conditions.
5.Construction of a diagnostic model based on random forest and artificial neural network for peri-implantitis
Haoran YANG ; Yuxiang CHEN ; Anna ZHAO ; Tingting CHENG ; Jianzhong ZHOU ; Ziliang LI
West China Journal of Stomatology 2024;42(2):214-226
Objective This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest(RF)and artificial neural network(ANN).Methods GSE-33774,GSE106090,and GSE57631 datasets were obtained from the GEO database.The GSE33774 and GSE106090 da-tasets were analyzed for differential expression and functional enrichment.The protein-protein interaction networks(PPI)and RF screened vital genes.A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets.A transcription factor-gene interaction network and a transcription factor-micro-RNA(miRNA)regulatory network were also established.Results A total of 124 differentially expressed genes(DEGs)involved in the regulation of peri-implantitis were screened.Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration.The PPI and RF screened six essential genes,namely,CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8.The receiver oper-ating characteristic curve(ROC)indicated that the ANN model had an excellent diagnostic performance.FOXC1,GA-TA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 may be a key miRNA.Con-clusion The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence,and CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8 are potential diagnostic markers.FOXC1,GATA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 plays a vital role as a critical miRNA.
6.Role of fatty acid metabolism-related genes in periodontitis based on machine learning and bioinformatics analysis
Yuxiang CHEN ; Anna ZHAO ; Haoran YANG ; Xia YANG ; Tingting CHENG ; Xianqi RAO ; Ziliang LI
West China Journal of Stomatology 2024;42(6):735-747
Objective This study aims to investigate the role of genes related to fatty acid metabolism in periodon-titis through machine learning and bioinformatics methods.Methods Periodontitis datasets GSE10334 and GSE-16134 were downloaded from the GEO database,and the fatty acid metabolism-related gene sets were obtained from the GeneCards database.Differentially expressed fatty acid metabolism-related genes(DEFAMRGs)in periodontitis were screened using the"limma"R package.Functional enrichment and pathway analyses were conducted.Recursive Feature Elimination,Least Absolute Shrinkage and Selection Operator,and Boruta algorithm were used to determine hub DEFAMRGs and construct diagnostic models with internal and external validation.Subtypes of periodontitis relat-ed to hub DEFAMRGs were constructed using consis-tency clustering analysis.CIBERSORT was used to ana-lyze immune cell infiltration in gingival tissues and ex-plore the correlation between hub DEFAMRGs and im-mune cells.Results A total of 113 periodontitis DE-FAMRGs were screened out as a result.The enrichment analysis results indicate that DEFAMRGs are mainly associat-ed with immune inflammatory responses and immune cell chemotaxis.Finally,8 hub DEFAMRGs(BTG2,CXCL12,FABP4,CLDN10,PPBP,RGS1,LGALSL,and RIF1)were identified and a diagnostic model(AUC=0.967)was con-structed,based on which periodontitis was divided into two subtypes.In addition,there is a significant correlation be-tween hub DEFAMRGs and different immune cell populations,with mast cells and dendritic cells showing higher cor-relation.Conclusion This study provides new insights and ideas for the occurrence and development mechanism of periodontitis and proposes a diagnostic model based on hub DEFAMRGs to provide new directions for diagnosis and treatment.