Cancer-testis gene-expression features in various tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14260-e14260
Author(s):  
Kristina I. Soldatova ◽  
Oleg Ivanovich Kit ◽  
Roman E. Tolmakh ◽  
Liubov Yu Vladimirova ◽  
Denis S. Kutilin
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcriptional Activity ◽  
Test Results ◽  
Cdna Synthesis ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Tumor Tissues ◽  
Real Time Qpcr ◽  
Cancer Testis

e14260 Background: Cancer-testis antigens (CTA) can be an effective target for immunotherapy. Immunotherapeutic approaches targeting CTA in breast cancer (BC), endometrial cancer (EC), ovarian cancer (OC), and colon cancer (CRC) are in the incipient stages of development. The purpose of our study was screening of CTA specific for BC, EC, OC and CRC, based on an analysis of transcriptional profiles of CT-genes. Methods: Tumor and intact tissues of the breast, uterus, ovaries and colon were studied in 35, 30, 20 and 60 patients, respectively. RNAs were isolated using the method described by Chomczynski and Sacchi (2006). The REVERTA-L reagent kit was used for the cDNA synthesis. Relative expression of 16 genes ( MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was determined by Real-Time qPCR (with GAPDH and GUSB as reference genes). Statistical analysis was performed using the Mann-Whitney test. Results: BC patients showed significantly (p < 0.005) increased expression of MAGEA3, MAGEA4 and GAGE3 in tumor tissues compared to normal ones; EC patients - significantly (p < 0.05) increased expression of MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SCP1 and PRAME1 in tumor tissues compared to normal ones; OC patients - significantly (p < 0.05) increased expression of MAGEB1, MAGEB2, GAGE1, NY-ESO1 and decreased expression of MAGEA3, MAGEA4, GAGE3, GAGE4, XAGE3, SSX2, SCP1 and PRAME1; CRC patients - significantly (p < 0.05) increased expression of SSX2 and PRAME1, together with decreased BAGE expression, in tumors compared to normal tissues. Conclusions: Analysis of the transcriptional activity of CT-genes revealed the most common diagnostic markers and immunotherapeutic targets for every malignancy: in BC - MAGEA3, MAGEA4 and GAGE3, in EC - MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SYCP1 and PRAME1, in OC - MAGEB1, MAGEB2, GAGE1 and NY-ESO, in CRC - SSX2 and PRAME1.

Expression of SSX-2 and SSX-4 Genes in Neuroblastoma

2002 ◽  
Vol 17 (4) ◽  
pp. 219-223 ◽  
Author(s):  
S.N. Chi ◽  
N.-K.V. Cheung ◽  
I.Y. Cheung
Keyword(s):  
Cytolytic T Lymphocytes ◽  
Rt Pcr ◽  
Normal Peripheral Blood ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Stage 4 ◽  
The Family ◽  
Prognostic Utility ◽  
Stage 1 ◽  
Cancer Testis

The SSX genes are members of the family of cancer/testis antigens that encode tumor-associated antigens recognizable by autologous cytolytic T lymphocytes. Their expression is common in tumors of diverse lineages and absent in normal tissues except testis and thyroid. In this study, sixty-seven neuroblastomas (NB) (12 stage 1, 13 stage 2, 12 stage 3, 12 stage 4S and 13 stage 4) were examined by RT-PCR and a sensitive chemiluminescent detection method for SSX-2 and SSX-4 expression. Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4. SSX-2 and SSX-4 positivity correlated with metastatic NB stage 4 (p=0.02 and p=0.006, respectively). Sensitivity experiments showed SSX-2 detection was one tumor cell in 106 normal cells, and one in 104 for SSX-4. All normal tissues (n=6), with the exception of testis, normal bone marrow (BM, n=12) and normal peripheral blood (PBL, n=10) were negative for SSX-2 and SSX-4 expression. Thirty-two BM and 14 PBL obtained from 35 stage 4 NB patients at 24 months from their diagnosis were evaluated for SSX-2 expression. Unlike another cancer/testis antigen, GAGE, only one BM sample was positive, and no prognostic utility could be established. Further investigation of SSX expression at other relevant time points is warranted.

scholarly journals Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Vinodh Kumar Radhakrishnan ◽  
Lorraine Christine Hernandez ◽  
Kendra Anderson ◽  
Qianwei Tan ◽  
Marino De León ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
African American Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Gene Imprinting ◽  
Vietnamese Women ◽  
Tumor Tissues ◽  
Incidence And Mortality ◽  
Caucasian Women

African American women suffer higher incidence and mortality of triple negative breast cancer (TNBC) than Caucasian women. TNBC is very aggressive, causing the worst clinical outcome. We previously demonstrated that tumors from these patients express high IGF-II and exhibit high activation of the IGF signaling pathways. IGF-II gene expression is imprinted (monoallelic), promotes tumor progression, and metastasis and regulates Survivin, a TNBC prognostic marker. Since BC mortality has increased among young Vietnamese women, we analyzed 48 (paired) TNBC samples from Vietnamese patients to assess IGF-II expression. We analyzed all samples by qrtPCR for identification of IGF-II heterozygosity and to determine allelic expression of the IGF-II gene. We also analyzed the tissues for proIGF-II and Survivin by RT-PCR and Western blotting. A total of 28 samples displayed IGF-II heterozygosity of which 78% were biallelic. Tumors with biallelic IGF-II gene expression exhibited the highest levels of proIGF-II and Survivin. Although 100% of these tissues corresponding normal samples were biallelic, they expressed significantly lower levels of or no proIGF-II and Survivin. Thus, IGF-II biallelic gene expression is differentially regulated in normal versus tumor tissues. We propose that intratumoral proIGF-II is dependent on the IGF-II gene imprinting status and it will promote a more aggressive TNBC.

scholarly journals Identification of Potential Genes in Her2+ Breast Cancer by Co-expression Network Analysis

2020 ◽  
Author(s):  
Xinyang Li ◽  
Yukun Wang ◽  
Ziming Wang ◽  
Ge Yao ◽  
Jiahao Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Network Analysis ◽  
Growth Factor Receptor ◽  
Gene Expression Omnibus ◽  
Oxidoreductase Activity ◽  
Scale Free ◽  
Software Analysis ◽  
Normal Tissues ◽  
Her2 Breast Cancer

Abstract Background Breast cancer (BC) is one of the most common malignancies in women all over the world. For patients with human epidermal growth factor receptor 2 positive (Her2+) BC, although the widespread use of anti-Her2 therapy has make for survival increased, improved survival has led to an increased demand for better management and diminish toxic side effects of anticancer treatments. This study aimed to identify the potential biomarkers associated Her2 + BC in order to improve the overall management of BC treatment. Results Our research downloaded GSE54140 gene expression datasets from the Gene Expression Omnibus data sets, and used weighted gene co-expression network analysis (WGCNA) to developed a scale-free gene co-expression network to explore the associations between gene sets and clinical features. A total of 60 modules were analyzed, and found that the skyblue3 module was significantly related to Her2 + BC. The function of 93 genes in the skyblue3 module was annotated by DAVID bioinformatics tool, and it was demonstrated that the function of the module was mainly related to nuclear-transcribed mRNA catabolic process, cytosol, and oxidoreductase activity. Based on the WGCNA and Cytoscape software analysis, 9 hub genes (PGAP3, PPP1R1B, PNMT, ERBB2, CISD3, CRKRS, TCAP, STARD3, and NEUROD2) were identified. The Human Protein Atlas database detected that the protein level of PGAP3, PPP1R1B, PNMT, ERBB2, CISD3, CRKRS, TCAP, and STARD3 in tumor tissues were different from normal tissues. And survival analysis shows that PGAP3, PNMT, ERBB2, TCAP, and STARD3 were negatively associated with the overall survival (P < 0.05). Conclusions In total, 9 candidate biomarkers were identified by comprehensive analysis, among which, the co-expansion of PGAP3, CRKRS, STARD3 and NEUROD2 related to ERBB2 may be associated with the occurrence of Her2 + BC. In addition, PPP1R1B, CRKRS and TCAP are related to drug resistance and adverse reactions in the treatment of Her2 + BC.

scholarly journals Study of KMT2B (MLL2) gene expression changes in patients with breast cancer

2019 ◽  
Vol 8 (2) ◽  
pp. BMT24
Author(s):  
Mohammad Ghanbari ◽  
Mohammadali Hosseinpour-Feizi ◽  
Reza Safaralizadeh ◽  
Aida Aghazadeh ◽  
Vahid Montazeri
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Tissue ◽  
Rna Extraction ◽  
Cancer Tissue ◽  
Cdna Synthesis ◽  
Tissue Samples ◽  
Spss Software ◽  
Analyze Data ◽  
Mll2 Gene

Aim: This study aimed to demonstrate misregulation of KMT2B gene expression in breast cancer tissue. Materials & methods: Cancerous and marginal tissue samples were collected from 43 female patients. After RNA extraction and cDNA synthesis, quantitative-PCR was used to evaluate the expression level of the KMT2B gene. REST, Sigma plot and SPSS software were used to analyze data. Results: KMT2B gene expression was significantly decreased in tumor tissue compared with marginal tissue (p = 0.02). No significant correlation was found between expression levels of KMT2B and clinical parameters of patients (p > 0.05) Conclusion: Our study demonstrated that downregulation of KMT2B is associated with breast cancer and its misregulation may play an important role in tumorigenesis.

Some characteristics of cancer-testis gene expression regulation in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14233-e14233
Author(s):  
Kristina I. Soldatova ◽  
Oleg Ivanovich Kit ◽  
Roman E. Tolmakh ◽  
Denis S. Kutilin
Keyword(s):  
Colorectal Cancer ◽  
Cluster Analysis ◽  
Copy Number ◽  
Dna Methyltransferase ◽  
Gene Expression Regulation ◽  
Strong Positive Correlation ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Cancer Testis

e14233 Background: Cancer-testis antigens (CTA) can be used in immunotherapy and for early detection of cancer. Despite numerous studies of the CTA expression in different tumors, their transcriptional activity and its regulation in colorectal cancer (CRC) remain poorly understood. The purpose of the study was to analyze the expression of cancer-testis genes (CT-genes) and mechanisms of its regulation in CRC. Methods: Tumor and intact tissues of the colon were studied in 60 patients. RNAs were isolated using the method described by Chomczynski and Sacchi (2006). The REVERTA-L reagent kit was used for the cDNA synthesis. Expression of 16 CT-genes (MAGE-A1, -A2, -A3, -A4, MAGE-B1, -B2, GAGE-1, -3, -4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) and expression and copy number of 3 DNA methyltransferase genes (DNMT1, DNMT3A, DNMT3B) were determined by Real-Time qPCR (GAPDH and GUSB - reference genes). For the cluster analysis, we used our R scripts. Differences were assessed by the Mann-Whitney test, and correlations – by the Spearman's rank correlation coefficient (r). Results: The expression of 2 CT genes, SSX2 and PRAME1, was increased (p < 0.05) by 1.8 and 2.9 times, respectively, and the BAGE expression was decreased by 2.4 times in tumor tissues, compared to the normal tissues. The expression and copy number of DNMT3A in tumor tissues was 1.5 and 2 times higher (p < 0.05), and that of DNMT3B – 2 times lower (p < 0.005), compared to normal tissues. The copy number and expression of the DNMT1 gene did not change. A strong positive correlation (r = 0.996) between the expression and copy number of DNA methyltransferase genes was observed. Using cluster analysis (Hierarchical Clustering, Euclidean distance), we detected two clusters of CRC samples different in the expression of CT-genes and methyltransferases. Cluster 1 showed increased expression of DNMT1, DNMT3A and DNMT3B and decreased expression of BAGE, SSX2 and PRAME1; cluster 2 – decreased expression of DNMT1, DNMT3A and DNMT3B and increased expression of BAGE, SSX2 and PRAME1. Conclusions: The detected aberrant expression of the CT-genes BAGE, SSX2, PRAME1 in CRC depends on the expression of DNMT1, DNMT3A, DNMT3B, which in its turn depends on the copy number of the corresponding DNA methyltransferase genes.

Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4733-4733 ◽  
Author(s):  
Valéria C.C. Andrade ◽  
André L. Vettore ◽  
Manuella S.S. Almeida ◽  
José S.R. Oliveira ◽  
Maria de Lourdes L.F. Chauffaille ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Three Samples ◽  
Cox's Regression ◽  
Ct Antigens ◽  
Cancer Testis

Abstract Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.

scholarly journals MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction

2018 ◽  
Vol 47 (5) ◽  
pp. 2147-2158 ◽  
Author(s):  
Feiyu Chen ◽  
Na Luo ◽  
Yu Hu ◽  
Xin Li ◽  
Kejing  Zhang
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Tumor Development ◽  
Cancer Stemness ◽  
Normal Tissues ◽  
Tumor Tissues

Background/Aims: Triple negative breast cancer (TNBC) is resistant to conventional chemotherapy due to high proportions of cancer stem cells (CSCs). The aim of this study is to unravel the miR-137-mediated regulatory mechanism of B-cell lymphoma/leukemia 11A (BCL11A) in TNBC. Methods: A corhort of 34 TNBC tumor tissues and paired adjacent normal tissues, as well as 25 non-TNBC tumor tissues and paired adjacent normal tissues were collected post-operatively from patients with breast cancer. Q-PCR was performed to determine the mRNA levels of miR-137 and BCL11A in breast tissues and cell lines. Bioinformatics analysis and dual luciferase reporter assay were used to verify the direct interaction between miR-137 and BCL11A. After up-/down-regulation of BCL11A, miR-137, or DNMT1 via lentiviral transduction in TNBC cell lines SUM149 and MDA-MB-231 cells, Q-PCR and Western blot assays were used to detect the expression levels of BCL11A, DNA methyltransferases 1 (DNMT1), and Islet-1 (ISL1). Mammosphere assay was conducted to assess tumorosphere formation ability of cells, coupled with flow cytometry to determine the percentage of breast cancer stem cells. Co-immunoprecipitation assay was used to determine the interaction between BCL11A and DNMT1. Xenograft tumorigenesis assay was performed to monitor tumor formation in vivo. Results: BCL11A was highly expressed in TNBC, whereas miR-137 was significantly lower in both TNBC tissues and cell lines. miR-137 suppressed BCL11A expression at both mRNA and protein levels by directly targeting its 3’UTR. In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of BCL11A reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. Furthermore, BCL11A interacted with DNMT1 in TNBC cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing ISL1 expression both in vitro, and in vivo. Conclusions: By perturbing BCL11A-DNMT1 interaction, miR-137 impairs cancer stemness and suppresses tumor development in TNBC.

scholarly journals Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis

Tumor Biology ◽  
2017 ◽  
Vol 39 (8) ◽  
pp. 101042831769836 ◽  
Author(s):  
Fereshteh Ahmadinejad ◽  
Seyed Javad Mowla ◽  
Mohammad-Amin Honardoost ◽  
Mostafa Gholami Arjenaki ◽  
Mohammad Moazeni-Bistgani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
In Silico ◽  
Breast Tumors ◽  
Normal Tissues ◽  
Node Metastases ◽  
Lower Expression

Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.

scholarly journals Expression of MAGE-A and NY-ESO-1 cancer/testis antigens in medullary breast cancer: a retrospective immunohistochemical study

2011 ◽  
Vol 52 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Božica Matković ◽  
Antonio Juretić ◽  
Giulio C Spagnoli ◽  
Viktor Šeparović ◽  
Marija Gamulin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immunohistochemical Study ◽  
Cancer Testis Antigens ◽  
Medullary Breast Cancer ◽  
Cancer Testis
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