Journal: Nature Communications

Article Title: Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity

doi: 10.1038/s41467-024-53877-z

Figure Lengend Snippet: A IMPDH2 shown in red, scored as an interactor of PARP1 and TOP2A DNA damage effectors (from OpenCell resource). Purine pathway enzymes are shown in orange, rest of metabolic enzymes in yellow. B Western blot of the chromatin fraction from MDA-MB-231 cells of IMPDH2 and IgG immunoprecipitation showing PARP1 and TOP2A pull-down after 3 h of 1 μM etoposide treatment and 24 h release, experiment performed twice with similar results. C Western blot of the nuclear-enriched fraction from Hs 578T cells of IMPDH2 and IgG immunoprecipitation showing IMPDH2, PARP1 and TOP2A, experiment performed twice with similar results. Western blot of MDA-MB-231 cells WT ( D ) and KO ( E ) showing full PARP1 and apoptotic and necrotic PARP1 cleaved, experiment performed twice; tubulin was used as a loading control. F Quantification of nuclear NAD+ as YFP/mCherry ratio across cell cycle phases in WT and KO cells cultured in the presence of guanosine 400 μM (WT: n G1 = 2316, n S = 1348, n G2/M = 1761; KO: n G1 = 2747, n S = 1359, n G2/M = 1282; outliers removed, 3 SD; unpaired two-tailed Wilcoxon test). Measurement of total cell death ( G ) and early apoptosis, late apoptosis/necrosis ( H ) in MDA-MB-231 WT and KO cells without guanosine supplementation for 96 h (WT: n = 6; KO: n = 6; unpaired two-tailed t-test); mean values +/− SD. Quantification of total cytosolic cleaved Casp3 Spot Area ( I ) (nWT= 79460, nKO= 7453; outliers removed, 3 SD; unpaired two-tailed Wilcoxon test), PARP1 cytosolic intensity ( J ) (nWT= 41640 nKO= 2297; outliers removed, 3 SD; unpaired two-tailed Wilcoxon test) and nuclear poly/mono ADP-ribose signal intensity ( K ) ( n WT = 32600, n KO = 364; unpaired two-tailed Wilcoxon test) in MDA-MB 231 WT and KO cells without guanosine supplementation for 96 h. Immunofluorescence of PARP1 representative pictures (magenta) and DAPI (blue) in DMSO control and 10 μM etoposide treatment after 24 h of release; non-confocal mode, scale bar 15μm ( L ) and number of PARP1 spots quantification in MDA-MB-231 cells (DMSO, n = 3748; n 1μM = 3165; n 2.5 μM = 3763; n 5μM = 2898; n 10μM = 3740; unpaired two-tailed Wilcoxon test) ( M ). All box plots indicate the median value (central line), interquartile range IQR (box boundaries), and up to 1.5*IQR beyond the box boundaries (whiskers). Source data are provided as a Source Data file.

Article Snippet: Protein interactors of TOP2A and PARP1 were derived from the OpenCell project .

Techniques: Western Blot, Immunoprecipitation, Control, Cell Culture, Two Tailed Test, Immunofluorescence

Journal: Nature Communications

Article Title: Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity

doi: 10.1038/s41467-024-53877-z

Figure Lengend Snippet: A , B Western blot analysis of PARP1 fragmentation in WT, KO-WT, and KO-NLS treated with DMSO or etoposide without release and after 24 h release (experiments performed twice). Tubulin is used as loading control. Immunofluorescence pictures of IMPDH2 (green), DAPI (blue), and PARP1 (magenta) from DMSO and 10 μM 24 h etoposide treatment, scale bar 15μm ( C ), and quantification of cytosolic PARP1 spots in KO-WT and KO-NLS cells normalized by DMSO (DMSO, nKO-WT = 75011; nKO-NLS = 125677, n10μM KO-WT = 45449; n10μM KO-NLS = 75939). Unpaired two-tailed Wilcoxon test, ( n = 3 and 3 technical replicates per condition) ( D ). Immunofluorescence pictures of Phalloidin (red), cleaved Caspase3 (yellow) and DAPI (blue) from DMSO and 10μM 24 h etoposide treatment, scale bar 15 μm ( E ), and quantification of total cytosolic cleaved Caspase spot area in KO-WT and KO-NLS cells (DMSO, nKO-WT = 50568; nKO-NLS = 82455, n10μM KO-WT = 447736; n10μM KO-NLS = 80561). Unpaired two-tailed Wilcoxon test, ( n = 3 and 3 technical replicates per condition) ( F ). G Quantification of nuclear poly/mono ADP-ribose signal intensity in MDA-MB-231 WT, KO, KO-WT, KO-NLS cells in the absence of guanosine supplementation for 96 h (nWT = 32590, nKO= 4575, nKO-WT = 3798, nKO-NLS = 15868) ( n = 3 biological replicates, unpaired two-tailed Wilcoxon test). H Quantification of nuclear poly/mono ADP-ribose signal intensity for a titration with increasing NAD + concentrations in KO-WT and KO-NLS cells (nKO-NLS = 15868, n0 = 10376, n12.25 = 2194, n100 = 2965, nKO-WT = 3798; unpaired two-tailed Wilcoxon test); outliers removed, and constantly added to improve visualization. Quantification of intranuclear NAD + as YFP/mCherry ratio for KO-WT and KO-NLS cells with representative images (scale bar 15μm) after DMSO or 10 μM etoposide treatment for 2 h ( I ) and 24 h ( J ). Two-way Anova with either Tukey’s or Sidak multiple comparisons depending on intra or inter-comparison. For each timepoint 3 biological replicates were performed for the DMSO condition and 5 biological replicates for the ETO condition. All box plots indicate median value (central line), interquartile range IQR (box boundaries), and up to 1.5*IQR beyond the box boundaries (whiskers). Source data are provided as a Source Data file.

Article Snippet: Protein interactors of TOP2A and PARP1 were derived from the OpenCell project .

Techniques: Western Blot, Control, Immunofluorescence, Two Tailed Test, Titration, Comparison

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Serial archival sections representative of an IDC stained for H&E, TOP2A, MCM2 and BUB1B proteins. (a) Primary invasive ductal carcinoma (IDC) of the breast, grade 2, featuring focal tubular differentiation. (b, c, d) Distinct nuclear immunoreactivity for TOP2A marking the presence of cycling cells in about 15% of the infiltrating tumor cells, and for MCM2 marking the “licensed” population in about 1/3rd of the infiltrating tumor cells and diffuse cytoplasmic immunoreactivity (2+) with focal cell membrane accentuation for BUB1B protein (Immunoperoxidase staining (IMPOX staining); original magnifications 200x).

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Staining, Immunoperoxidase Staining

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Serial archival sections representative of histologically normal breast tissues with high-grade molecular abnormality stained for H&E, TOP2A, MCM2 and BUB1B proteins. (a) Portion of a TDLU from a histologically normal breast tissue with high-grade molecular abnormality (Case 22, specimen 1495). Serial sections showing the same TDLU as in (a) with distinct nuclear immunoreactivity for TOP2A (b) and MCM2 (c) in the epithelial cell nuclei, and diffuse cytoplasmic immunoreactivity (2+) for BUB1B protein (d) in the mammary epithelial cells. (IMPOX staining; original magnifications 400x).

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Staining

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Serial archival sections representative of a histologically normal breast tissues with low-grade molecular abnormality stained for H&E, TOP2A, MCM2 and BUB1B proteins. (a) Portion of a TDLU from a molecularly low-risk, histologically normal breast tissue (Case 8, specimen 1481). Serial sections showing the same TDLU as in (a) without any expression of TOP2A (b) and MCM2 (c) in the epithelial cell nuclei. There is a focal cytoplasmic immunoreactivity (1+ to 2+) for BUB1B protein (d) in some of the mammary epithelial cells in this field. (IMPOX staining; original magnifications 200x).

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Staining, Expressing

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Mean TOP2A and MCM2 indices and BUB1B protein expression scores in IDCs and molecularly high-risk and low-risk, histologically normal breast tissues.

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Expressing, Microarray

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Mean TOP2A index in independent test sets of histologically normal breast (including reduction mammoplasty tissues), histologically normal and benign breast tissues from patients without and with synchronous cancer, DCIS and invasive breast carcinoma tissues. There is an obvious trend toward increasing TOP2A expression from benign to malignant breast tissues.

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Expressing

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: TOP2A, MCM2, and BUB1B protein expression scores in IDCs, molecularly low-risk and molecularly high risk, histologically normal breast tissues.

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Expressing

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Immunohistochemical expresssion of TOP2A protein in HNB tissues with low-grade and high-grade molecular abnormalities and in IDCs. There is an obvious trend toward increasing expression from HNB tissues with low-grade molecular abnormality (white bars) to those with high-grade molecular abnormality (gray bars), and the IDCs (black bars), thus providing evidence for cross-platform validation of our original expression profiling data for TOP2A at the protein level. (a) Is the specimen-wise distribution of immunohistochemical expression of TOP2A for the HNB tissues with low-grade and high-grade molecular abnormality and IDC groups. (b) is the pairwise comparison of TOP2A immunostaining among the three groups. For each comparison (e.g., IDC versus normal), a mean difference with a 95% confidence interval (95% CI) is displayed to examine whether the difference is statistically significant (A 95% CI deviated away from 0 is statistically significant). The adjusted P value for each comparison, based on Tukey method, is shown.

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Immunohistochemical staining, Expressing, Immunostaining

Journal: Pathology Research International

Article Title: Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

doi: 10.4061/2011/489064

Figure Lengend Snippet: Immunohistochemical expression of TOP2A protein. (a) Histologically normal breast tissue from a reduction mammoplasty (RM) case featuring lack of nuclear expression of TOP2A in the epithelial cells lining a normal TDLU. (b) Histologically normal breast tissue from a patient with synchronous breast cancer showing positive nuclear staining in 4-5% of the mammary epithelial cells-higher TOP2A expression than the HNB tissues from a reduction mammoplasty case illustrated in (a). (c-d) A larger proportion of epithelial cells are immunoreactive for nuclear TOP2A protein in ductal carcinoma in situ (DCIS) and in the invasive ductal carcinoma (IDC) infiltrating the mammary fat. These cases illustrate an obvious increase in TOP2A protein expression from the lowest risk specimen from a reduction mammoplasty case (a), to the higher-risk specimens (c) and (d) (IMPOX staining for TOP2A; original magnifications 200x).

Article Snippet: The mouse monoclonal antibody that reacts with human TOP2A protein (#MS-1819-SO, Neomarkers) was used at a 1 : 50 concentration in Dako antibody diluent and incubated for 60 min.

Techniques: Immunohistochemical staining, Expressing, Staining, In Situ

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Conserved TOP2A (A) genes and (B) protein domains in different species.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques:

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: TOP2A mutations in all cancers from TCGA database. The cBioPortal tool was applied to analyze the mutation characteristics of TOP2A in the TCGA database, the (A) Genomic alteration frequencies and types; (B) genetic alteration frequencies (381/10953; 3%) and types of TOP2A gene in 10953 cancer patients with 10967 samples; (C) the alteration sites of TOP2A protein; (D) associations between the TOP2A alteration status of TOP2A with the overall survival, the disease-specific survival, the progression-free survival and the disease-free survival in OV patients were analyzed by the cBioPortal tool.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Mutagenesis

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: TOP2A gene and total protein expressions in different malignancies, pathological stages, and metastatic status. (A) Differently expressed TOP2A gene between various malignancies with/without specific malignant subtypes and the available normal control using the TIMER2 online tool based on TCGA database were presented as box plots (B) Differently expressed TOP2A gene between cancers of ACC, BRCA, DLBC, LAML, LGG, OV, PAAD, SARC, SKCM, THYM, UCS and TGCT from TCGA database and the available normal control from GTEx database were presented as box plots. * p < 0.01 (C) Differently expressed TOP2A total protein between primary cancer (LUAD, colon cancer, ovarian cancer, breast cancer, UCEC, and the clear cell RCC) and the paired normal tissues based on the CPTAC dataset. *** p < 0.001. (D) Representative immunohistochemistry images of TOP2A protein expressions in different cancer and normal control tissues from Human Protein Atlas (E) TNMplot for differently expressed TOP2A gene expressions in normal, cancerous, and metastatic cancerous tissues of breast, kidney, liver, lung, prostate, and skin (F) Boxplots showing TOP2A expression in stage-1, -2, -3 and -4 of ACC, BRCA, HNSC, KICH, KIRC, KIRP, LIHC, LUAD and LUSC with or without normal control based on TCGA database. * p < 0.05, ** p < 0.01; *** p < 0.001.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Control, Immunohistochemistry, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Prognostic association between TOP2A gene expression and survival of cancer patients based on TCGA database. GEPIA2 on line tool analyzed association between TOP2A gene expression with overall survival (A, B) , (A) Survival map of TOP2A gene with significant associations in ACC, KIRC, KIRP, LGG, LIHC, LUAD, MESO, and PAAD; (B) Survival curves of TOP2A gene with significant associations in ACC, CESC, KIRC, KIRP, LGG, LIHC, LUAD, MESO, PAAD, and THYM. GEPIA2 online tool analyzed the association between TOP2A gene expression with disease-free survival (C, D) , (C) Disease-free map of TOP2A gene with significant associations in ACC, KICH, KIRC, KIRP, LGG, LIHC, MESO, PAAD, PRAD, SARC, THCA, and UVM; (D) Disease-free survival curves of TOP2A gene with significant associations in ACC, KICH, KIRC, KIRP, LGG, LIHC, MESO, PAAD, PRAD, SARC, THCA, and UVM. (E) Correlation analysis between TOP2A gene expression and survivals (OS, DMFS, RFS, PPS, PFS, DSS, and FP) of cancer patients using Kaplan-Meier plotter. (F) The prognostic value of the TOP2A gene in renal cancer, liver cancer, pancreatic cancer, and lung cancer in the Human Protein Atlas dataset (HPA). High TOP2A group represents the high TOP2A expression group; the Low TOP2A group represents the low TOP2A expression group.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Gene Expression, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Phosphorylation level of TOP2A protein in various cancers. Expression levels of TOP2A protein with different phosphorylation sites (NP_001058.2, S1106, S1374, S1213, S1247, S1351, S1354, S1377, S1393, S1525, S1374S1377, S1351S1354 or T1343S1351S1354) between selected primary cancer and normal tissues analyzed by UALCAN on line tool based on the CPTAC dataset. Box plots for BRCA, LUAD, UCEC, COAD, KIRC, and OV.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Phospho-proteomics, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Association between TOP2A gene expression and tumor-immune cell infiltrates. (A) Correlations between the TOP2A expression with the abundance of cancer-associated fibroblasts in the estimation algorithms of EPIC, MCPCOUNT, and TIED; (B) associations of the TOP2A expression with the cancer-associated fibroblast infiltrates and the cancer purity; (C) correlations between the TOP2A expression with the abundance of Tregs in the estimation algorithms of CIBERSORT, CIBERSORT-ABS, and QUANTISEQ; (D) associations of the TOP2A expression with the Treg infiltrates and the cancer purity; (E) correlations between the TOP2A expression with the abundance of macrophage in the estimation algorithms of EPIC, TIMER and MCPCOUNT; (F) association of the TOP2A expression with macrophage infiltrates and the cancer purity.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Gene Expression, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Enrichment analysis of TOP2A -related genes. Experimentally confirmed TOP2A-binding proteins obtained using the STRING online tool under the setting of “no more than 50 interactors,” (A) PPI network with Cytoscape; (B) KEGG pathway analysis; (C) Gene Ontology (GO) analysis.

Article Snippet: As shown in , TOP2A protein was significantly upregulated in cancer than in normal control tissues, including breast, cervical, colon, endometrium, kidney, liver, lung, melanocytes, ovary, pancreas, thyroid gland, and testis, which were consistent with the expression panel of TOP2A mRNA in patients with same cancer based on TCGA database as shown in ; meanwhile, the data from CPTAC dataset was analyzed using the online UALCAN portal, which also showed an increased expression of TOP2A protein in patients with primary breast invasive carcinoma, ovarian serous cystadenocarcinoma, colon adenocarcinoma, uterine corpus endometrial carcinoma, and lung adenocarcinoma than in normal tissues, and consistent with the expression panel of TOP2A mRNA in patients with same cancer; however, TOP2A protein showed a lower expression in kidney renal clear cell carcinoma , which was inconsistent with the mRNA expression pattern in patients with kidney renal clear cell carcinoma based on TCGA database as shown in and protein expression pattern in patients with kidney renal clear cell carcinoma from the Human Protein Atlas (HPA) as shown in .

Techniques: Binding Assay

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Conserved TOP2A (A) genes and (B) protein domains in different species.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques:

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: TOP2A mutations in all cancers from TCGA database. The cBioPortal tool was applied to analyze the mutation characteristics of TOP2A in the TCGA database, the (A) Genomic alteration frequencies and types; (B) genetic alteration frequencies (381/10953; 3%) and types of TOP2A gene in 10953 cancer patients with 10967 samples; (C) the alteration sites of TOP2A protein; (D) associations between the TOP2A alteration status of TOP2A with the overall survival, the disease-specific survival, the progression-free survival and the disease-free survival in OV patients were analyzed by the cBioPortal tool.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Mutagenesis

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: TOP2A gene and total protein expressions in different malignancies, pathological stages, and metastatic status. (A) Differently expressed TOP2A gene between various malignancies with/without specific malignant subtypes and the available normal control using the TIMER2 online tool based on TCGA database were presented as box plots (B) Differently expressed TOP2A gene between cancers of ACC, BRCA, DLBC, LAML, LGG, OV, PAAD, SARC, SKCM, THYM, UCS and TGCT from TCGA database and the available normal control from GTEx database were presented as box plots. * p < 0.01 (C) Differently expressed TOP2A total protein between primary cancer (LUAD, colon cancer, ovarian cancer, breast cancer, UCEC, and the clear cell RCC) and the paired normal tissues based on the CPTAC dataset. *** p < 0.001. (D) Representative immunohistochemistry images of TOP2A protein expressions in different cancer and normal control tissues from Human Protein Atlas (E) TNMplot for differently expressed TOP2A gene expressions in normal, cancerous, and metastatic cancerous tissues of breast, kidney, liver, lung, prostate, and skin (F) Boxplots showing TOP2A expression in stage-1, -2, -3 and -4 of ACC, BRCA, HNSC, KICH, KIRC, KIRP, LIHC, LUAD and LUSC with or without normal control based on TCGA database. * p < 0.05, ** p < 0.01; *** p < 0.001.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Control, Immunohistochemistry, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Prognostic association between TOP2A gene expression and survival of cancer patients based on TCGA database. GEPIA2 on line tool analyzed association between TOP2A gene expression with overall survival (A, B) , (A) Survival map of TOP2A gene with significant associations in ACC, KIRC, KIRP, LGG, LIHC, LUAD, MESO, and PAAD; (B) Survival curves of TOP2A gene with significant associations in ACC, CESC, KIRC, KIRP, LGG, LIHC, LUAD, MESO, PAAD, and THYM. GEPIA2 online tool analyzed the association between TOP2A gene expression with disease-free survival (C, D) , (C) Disease-free map of TOP2A gene with significant associations in ACC, KICH, KIRC, KIRP, LGG, LIHC, MESO, PAAD, PRAD, SARC, THCA, and UVM; (D) Disease-free survival curves of TOP2A gene with significant associations in ACC, KICH, KIRC, KIRP, LGG, LIHC, MESO, PAAD, PRAD, SARC, THCA, and UVM. (E) Correlation analysis between TOP2A gene expression and survivals (OS, DMFS, RFS, PPS, PFS, DSS, and FP) of cancer patients using Kaplan-Meier plotter. (F) The prognostic value of the TOP2A gene in renal cancer, liver cancer, pancreatic cancer, and lung cancer in the Human Protein Atlas dataset (HPA). High TOP2A group represents the high TOP2A expression group; the Low TOP2A group represents the low TOP2A expression group.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Gene Expression, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Phosphorylation level of TOP2A protein in various cancers. Expression levels of TOP2A protein with different phosphorylation sites (NP_001058.2, S1106, S1374, S1213, S1247, S1351, S1354, S1377, S1393, S1525, S1374S1377, S1351S1354 or T1343S1351S1354) between selected primary cancer and normal tissues analyzed by UALCAN on line tool based on the CPTAC dataset. Box plots for BRCA, LUAD, UCEC, COAD, KIRC, and OV.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Phospho-proteomics, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Association between TOP2A gene expression and tumor-immune cell infiltrates. (A) Correlations between the TOP2A expression with the abundance of cancer-associated fibroblasts in the estimation algorithms of EPIC, MCPCOUNT, and TIED; (B) associations of the TOP2A expression with the cancer-associated fibroblast infiltrates and the cancer purity; (C) correlations between the TOP2A expression with the abundance of Tregs in the estimation algorithms of CIBERSORT, CIBERSORT-ABS, and QUANTISEQ; (D) associations of the TOP2A expression with the Treg infiltrates and the cancer purity; (E) correlations between the TOP2A expression with the abundance of macrophage in the estimation algorithms of EPIC, TIMER and MCPCOUNT; (F) association of the TOP2A expression with macrophage infiltrates and the cancer purity.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Gene Expression, Expressing

Journal: Frontiers in Genetics

Article Title: Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis

doi: 10.3389/fgene.2022.856692

Figure Lengend Snippet: Enrichment analysis of TOP2A -related genes. Experimentally confirmed TOP2A-binding proteins obtained using the STRING online tool under the setting of “no more than 50 interactors,” (A) PPI network with Cytoscape; (B) KEGG pathway analysis; (C) Gene Ontology (GO) analysis.

Article Snippet: To further evaluate the differences in TOP2A protein (NP_001058.2) expression between normal and tumor tissues, the protein expression patterns of TOP2A in cancer patients were first extracted from the Human Protein Atlas (HPA).

Techniques: Binding Assay