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Objective To investigate the relationship between DNA topoisomerase Ⅱ α (TOP2A) gene expression and clinicopathological characteristics and its significance of prognostic evaluation for patients with bladder cancer.Methods Bladder cancer gene expression profile GSE13507 (n =165) and GSE31189 (n =52) were obtained.The expression profile and clinical information of patients with bladder cancer were retrospectively analyzed,and the survival analysis was made.Gene set enrichment analysis (GSEA) was conducted to explore the related pathways which were regulated by TOP2A.Results Compared with normal bladder tissues,TOP2A was upregnlated in bladder cancer tissues (5.823 ± 1.079 vs.4.820 ± 1.129),with a statistically significant difference (t =4.336,P ＜ 0.001).The TOP2A gene expression in patients with bladder cancer was correlated with the age of patients (x2 =5.926,P =0.015),sex (x2 =6.046,P =0.014),T staging (x2 =19.484,P ＜ 0.001),N staging (x2 =9.178,P =0.002),M staging (x2 =21.142,P ＜ 0.001),tumor grade (x2 =47.005,P ＜ 0.001),and progression (x2 =11.735,P =0.001),but it was not correlated with recurrence (x2 =0.808,P =0.369).Survival analysis showed that the specific survival rate in the 100 months of TOP2A gene high expression group and low expression group had a statistically significant difference (66.59％ vs.87.95％,x2 =15.820,P ＜ 0.001).The median overall survival time of TOP2A gene high expression group and low expression group were 51.77 months and 134.97 months respectively,with a statistically significant difference (x2 =11.280,P =0.008).The results of GSEA indicated that TOP2A could regulate gene sets related with several pathways like MYC-V1 signaling (P =0.035,FDR =0.132),MYC-V2 signaling (P =0.012,FDR =0.058),E2F signaling (P ＜ 0.001,FDR =0.006) and G2M checkpoint (P =0.006,FDR =0.044).Conclusion The TOP2A gene expression is closely related with clinicopathological characteristics of patients with bladder cancer.TOP2A may function as a potential marker of prognosis for patients with bladder cancer.
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Objective To analyze the expression of programmed death ligand 1 (PD-L1),p16 proteins and DNA topoisomerase Ⅱ α (TOPO Ⅱ α) in cervical cancer and their clinical significances.Methods A total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma,30 high grade cervical intraepithelial neoplasia (CIN),30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015.An immunohistochemical EnVision method was used to detect the expression of PD-L1,p16 and TOPO Ⅱ α.Results The positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0 ％ (70/106),but it was not expressed in high grade CIN,low grade CIN and normal cervical tissues,the differences were statistically significant (all P =0.000).Whereas,in squamous cell carcinoma,the positive rate of PD-L1 in poor differentiation group [77.3 ％ (51/66)] was higher than that in middle or high differentiation group [56.5 ％ (21/40)],and the difference was statistically significant (x2 =7.02,P =0.01).According to the FIGO stage,the positive rate in stage Ⅰ-Ⅱ group [54.9 ％ (28/51)] was lower than that in stage Ⅲ-Ⅳ group [76.4 ％ (42/55)],and the difference was statistically significant (x2 =5.47,P =0.02).But there was no statistical significance in lesion size or lymph node metastasis (both P ＞ 0.05).The positive rate of p16 in cervical squamous cell carcinoma was 99.1％ (105/ 106),in high grade CIN was 86.7 ％ (26/30),in low grade CIN was 26.7 ％ (8/30),and no expression in normal cervical tissues,the differences were statistically significant (all P ＜ 0.001).The expression of p16 had no relationship with histological differentiation,FIGO stage,lesion size,and lymph node metastasis (all P ＞ 0.05).The positive expression rate of TOPO Ⅱ α in cervical squamous cell carcinoma was 97.2 ％ (103/106),compared with that in high grade CIN [73.3 ％ (22/30)],low grade CIN [66.7 ％ (20/30)],and normal cervical tissues (no expression),the differences were statistically significant (all P =0.000).But there was nosignificant difference in the positive expression rate of TOPOⅡ α between high grade and low grade CIN (x2 =0.32,P =0.570).The expression of TOPO 1Ⅱ α had no relationship with histological differentiation,FIGO stage,lesion size and lymph node metastasis (all P ＞ 0.05).Conclusion The expression of PD-L1,p16 and TOPO Ⅱ α is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer.
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Objective To probe into the content of DNA Topo Ⅱ in osteosarcoma after chemotherapy.Methods 30 patients with osteosarcoma received two courses of chemotherapy treatment before the surgical resection of the tumor tissue.Then immunohistochemistry was used to detect the content of Topo Ⅱ in tissues and detected its relationship in pathology.Results There were 8 out of 30 cases in which Topo Ⅱ was presented positive in osteosarcoma (26.7 ％).The protein content of Topo Ⅱ was unrelated to the patient' s age,gender,degree of tumor malignancy,tumor location and translocation or Enneking staging (P ＞ 0.05),but related to patients survival rate (P ＜ 0.05).Conclusion Patients with lower expression of Topo Ⅱ are more likely to have poor prognosis.
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Objective To explore the expressions of Topo-Ⅱ,GST-π in gastric cancer tissues and normal gastric mucosa tissues,to reveal its relationship with clinical pathological features and significance.Methods Immunohistochemical method was used to detect Topo-Ⅱ,GST-π expressions in 100 cases of gastric carcinoma and 20 cases of normal gastric mucosa,make a comprehensive analysis combined with clinical pathology data.Results There were significant difference of expression of Topo-Ⅱ,GST-π between the normal gastric mucosa tissues and gastric cancer of different degree of differentiation.Topo-Ⅱ positive expression rate of 5.0 ％ (1/20),100 ％ (30/30),96.7 ％ (29/30) and 87.5 ％ (35/40) respectively; GST-π positive expression rate were 60.0 ％ (12/20),83.3 ％ (24/30),96.7 ％ (29/30) and 100.0 ％ (40/40) respectively (P ＜ 0.05).The expressions of Topo-Ⅱ,GST-π in gastric cancer tissue were not relevant to patient' s sex,age,tumor location,infiltration depth (P ＞ 0.05).Topo-Ⅱ associated with the differentiation degree and lymph node metastasis of tumors,with the decreasing degree of tumor differentiation,lymph node metastasis,Topo-Ⅱ expression also decreased.GST-π was associated with tumor diameter,degree of differentiation and lymph node metastasis,the lower the degree of differentiation,lymph node metastasis,tumor diameter the more,GST-π expression increased (P ＜ 0.05).GST-π and Topo-Ⅱ were negative correlation and both expressed in gastric cancer tissue (P ＜ 0.01).Conclusions The expressions of Topo-Ⅱ in gastric cancer tissue is associated with the differentiation degree and lymph node metastasis of the tumor.GST-π is associated with tumor diameter,the degree of differentiation and lymph node metastasis.GST-π and Topo-Ⅱ in gastric cancer tissues are negatively correlated.
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Objective To investigate the binding capacities of two variants of quinolone resistance-determining region in the DNA gyrase subunit A to substrates in Klebsiella pneumonia (K.pneumonia).Methods Tertiary structures of two variants (type Ⅰ and type FH) of quinolone resistance-determining region in the DNA gyrase subunit A in K.pneumonia were predicted by homology modeling referring to that of wild type.Then,DOCK module in ArgusLab 4.1 software was used to perform molecular docking of two variants and wild type to seven kinds of quinolones substrates,and calculate binding free energies (△G).Moreover,numbers and distances of interaction between amino acid residues of DNA gyrase subunit A and ciprofloxacin were calculated.Results Molecular docking showed that binding free energies of type Ⅰ and type FH to pipemidic acid,ciprofloxacin,gatifloxacin were-26.607 50,-29.530 39,-29.493 09 kJ/mol and-26.696 44,-28.972 83,-29.590 50 kJ/mol,respectively,which declined greater than those of wild type (-27.188 82,-30.872 00 and-30.244 04 kJ/mol,respectively) and showed drug resistance.While binding free energies of type Ⅰ and type FH to levofloxacin were-29.013 81 and-29.497 57kJ/mol,respectively,and that of wild type was-28.016 20 kJ/mol.The binding free energies of type Ⅰ and type FH to nalidixic acid,norfloxacin,ofloxacin increased or declined.Moreover,if distance was less than 5 angstroms,atom pairs formed between wild type of DNA gyrase subunit A and ciprofloxacin had 16 pairs,while type Ⅰ and type FH had 2 pairs and 4 pairs,respectively.If distance was less than 4 angstroms,atom pairs formed between wild type and ciprofloxacin had 8 pairs,while type Ⅰ and type FH had no atom pairs.Conclusion Decline of binding capacities of two variants of DNA gyrase subunit A in K.pneumonia to ciprofloxacin played a role in drug resistance.
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Objective To determine the relationship between expression of topoisomerase Ⅱ α and clinicopathological factors,overall survival in colorectal caner.Methods Expression of topoisomerase Ⅱ α was measured using EnVision immunohistochemistry in 490 colorectal cancer patients.The relationship between topoisomerase Ⅱ α expression and various clinicopathological parameters was analyzed.Kaplan-Meier analyses and multivariate analyses were used to evaluate the significance of topoisomerase Ⅱ α expression in prognosis prediction.Results Overexpression of topoisomerase Ⅱ α was found to be related with lower T stage ( P =0.042 ),lower N stage ( P =0.038 ),and possibly with lower recurrence rate ( P =0.053 ).Kaplan- Meier analyses showed that overexpression of topoisomerase Ⅱ α was related with prolonged overall survival (P =0.022 ) and prolonged disease-free survival ( P =0.036).Multivariate analyses showed that elevated serum CEA ( P ＜ 0.001 ),elevated serum CA199 ( P =0.002 ),poor differentiation ( P =0.001 ),advanced Dukes stage ( P ＜ 0.001 ) and lower expression of topoisomerase Ⅱ α( P =0.017 ) were independent predictive factors for poor prognosis.Conclusions Expression of topoisomerase Ⅱ α is a favorable predictive factor for colorectal cancer,and would be useful in prognosis prediction and treatment selection for early colorectal cancer and malignant colorectal polyps,especially when it is used in combinations with serum CEA,CA199 and differentiation.
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Anthracycline-based chemotherapeutic agents were extensively applied to the treatment of breast cancer. The relation of its response to TOP2A gene was proved by a number of clinical studies demonstrating that patients with both HER2 gene amplification and TOP2A gene aberration have a favored outcome,but a consensus was not yet achieved.
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Protocarcinogenic gene Her-2/neu was closely related to the development of gastric cancer. Herceptin is an antibody according to Her-2/neu and is used for treating breast cancer. Topo Ⅱ α is the important Nuclear enzymes needed by DNA duplicate, and is closely related to the proliferation of malignant tumors, so it is the important target enzymes of cancer chemotherapy. Her-2/neu and Topo Ⅱ α are located in the same chromosomes, there are correlation between the two genes' proliferation or loss. We reviewed the expression of Her-2/neu and Topo Ⅱ α in the stomach and the new progress of the correlation between the two genes home and abroad in this paper, which provides new methods for the prevention and treatment of gastric cancer.
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Objective To investigate the expression of MIB1 and Topo Ⅱα,and their relation to the clinical grades and biological behavior in diffuse large-B cell lymphoma(DLBCL).Methods 66 csses of DLBCL were selected from the Pathological Department of Shanxi Tumor Hospital from 1996 to 2001.An ABC method was used to detect the expression of CD3,CD20,CD79α,Pax5,and a double immunostaining technique ABC-DAB/SABAP-vector red and ABC-DAB/immunogolden was used to detect the expression of MIB1 and Topo Ⅱα.Results Expression of MIB1 and Topo Ⅱα were increased along with the clinical stage of the DLBCL.There was a significant difference between ealier stage(Ⅰ,Ⅱ)and later stage(Ⅲ,Ⅳ)in DLBCL(P＜0.05).The expression of MIB1 and Topo Ⅱα were also significantly related to the survival rate(r=-0.487,0.251 respectively,P＜0.05).Conclusion Expression of MIB1 and Tope Ⅱα may serve as two independent prognostic predictors in DLBCL.
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25%) and low LI groups (positive cell rate ≤25%) of TopoⅡ? and Ki-67. However, in high LI groups, the overall survival rate was lower than those in low LI groups (P=0.002, P=0.004, Log-Rank test), the volume of recurred masses was bigger (P=0.005, P=0.000) and recurrence time was shorter (P=0.000, P=0.000) than those in low LI groups. There existed a significant linear correlation between the expressions of TopoⅡ? and Ki-67 (r=0.935 5, P=0.000). The expressions of TopoⅡ? and Ki-67 were related with pathological category and staging (P0.05). Conclusions Both TopoⅡ? and Ki-67 could be used as specific markers of cell proliferation, but the specificity of TopoⅡ? might be higher than that of Ki-67 in accurately reflecting the cell proliferation. TopoⅡ?, combined with pathological category and staging, may play an important role in prognostic prediction of uterine sarcoma.