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Background: Cancer testis antigens (CTA) are normally expressed in immune privileged tissues such as the testis. They are considered tumor-associated antigens because they are specifically expressed in different cancers. Their distinct nature rendered them appealing targets for cancer diagnosis, prognosis. and immunotherapy. We aimed to identify the association of two CTA genes with colon cancer (CC) in a cohort of Egyptian patients. Methods: We measured the relative gene expression levels of two CTAs: SPAG9 and FBXO39 in colonic tumor tissue and adjacent normal-appearing mucosa in 50 newly diagnosed colon cancer patients by real-time reverse transcription polymerase chain reaction. Gene expression was also studied in relation to demographic and pathological criteria. Results: SPAG9 and FBXO39 were overexpressed in 22% and 40% of cases, respectively. Overexpression of both genes was evident in 14% of cases. We report the significant expression of FBXO39 (P < 0.01) in tumor tissue compared to normal tissue. SPAG9 was significantly increased in large sized tumors compared to smaller sized tumors. Otherwise, there was no significant association between gene expression and the evaluated clinicopathological features (P > 0.05). Conclusions: SPAG9 and FBXO39 are possible CC diagnostic biomarkers. Further studies are warranted to validate our findings.
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@#[Abstract] Objective: To investigate the expression of MAGE-C1 (melanoma-associated antigen-C1) in breast cancer tissues and its correlation with clinicopathological features and prognosis of breast cancer patients. Methods: Breast cancer tissues, normal breast tissues and benign breast lesion tissues (60 samples for each) were collected from the Fourth Hospital of Hebei Medical University during January 2008 and December 2008.The mRNA and protein expressions of MAGE-C1 in three types of breast tissues were detected by RT-PCR and immunohistochemistry, and their correlation with clinicopathological parameters and prognosis of breast cancer patients were also analyzed. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) were used to treat breast cancer MDA-MB-231 and MCF-7 cells, and RT-PCR was used to determine the changes in mRNA expression of MAGE-C1 after drug treatment. Results: The positive expression rate of MAGE-C1 mRNA and protein in breast cancer tissues were 43.3% (26/60) and 38.3% (23/60), respectively; and the mRNA and protein expressions of MAGE-C1 were all negative in normal breast tissues and benign breast lesion tissues. MAGE-C1 expression was positively associated with high tumor grade (χ2 =6.233, P<0.05). Recurrence-free survival (RFS) of patients with negative MAGE-C1 expression was significantly longer than those patients with positive MAGE-C1 expression (χ 2 =4.213, P<0.05). MAGE-C1 expression (HR=3.980, P<0.05) and clinical stage (HR=3.637, P<0.05) could be used as independent prognostic factors for breast cancer patients. 5-Aza-CdR and/or TSA treatment had no significant influence on MAGE-C1 gene expression (P>0.05). Conclusion: MAGE-C1 is a tumor-specific antigen and its expression is associated with poor prognosis of breast cancer patients.
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Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.
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Objective To investigate the expression of melanoma antigen- encoding gene (MAGE) A1 protein in esophageal squamous cell carcinoma, and explore its correlation with the clinicopathological factors and prognosis. Methods A retrospective analysis was performed on 197 patients with esophageal squamous cell carcinoma who accepted radical surgical treatment from January 2006 to December 2012. The expressions of MAGEA1 protein in these specimens of cancer tissue and cancer adjacent tissue were detected by immunohistochemistry with tissue microarray technology. Results MAGEA1 protein was expressed in cytoplasm and nucleus of tumor cells. The positive expression rate of MAGEA1 protein in cancer tissue was significantly higher than that in cancer adjacent tissue: 73.6％ (145/197) vs. 5.6％ (11/197), and there was statistical difference (P<0.01). The positive expression of MAGEA1 protein had no correlations with sex, age, history of smoking/drinking, family history of upper gastrointestinal cancer, depth of tumor invasion, lymph node metastasis, tumor differentiation, location and TNM stage (P>0.05). Kaplan-Meier survival analysis result showed that the 5-year survival rate in patients with MAGEA1 protein positive expression was significantly lower than that in patients with MAGEA1 protein negative expression (37.2％ vs. 53.8％), and there was statistical difference (P=0.018). Multivariate analysis result showed that MAGEA1 protein positive expression was an independent predictor of prognosis in esophageal squamous cell carcinoma patients (HR=1.91, 95％CI 1.22 to 2.98, P = 0.004). Conclusions The expression of MAGEA1 protein is abundant in esophageal squamous cell carcinoma, and is related to worse clinical outcome. MAGEA1 protein could be a candidate target for tumor immunotherapy.
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Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer (PCA). Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCA, especially patients with low-risk disease.
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Objective To investigate the expression level and clinical significance of melanoma antigen gene A (MAGEA) in osteosarcoma patients. Methods Compare gene expression profiles in osteosarcoma cell lines and osteoblasts with gene microarrays. Validation of differentially expressed genes was carried out by real-time polymerase chain reaction analysis. Corresponding protein levels were measures by Western blot analysis in osteosarcoma cell lines and by immunohistochemistry in osteosarcoma tissues. The staining intensity of immuno-histochemistry was correlated with clinical outcome , and its prognostic significance was analyzed. Results Sev-eral genes belonging to MAGEA increased significantly in all osteosarcoma cell lines and tumor tissue , but not in normal osteoblast cell. Patients with MAGEA expression has higher risk of lung metastasis (relative risk 2.79, 95% confidence interval, 1.12-6.93; P = 0.028) and lower five-year survival rates (39.6% ± 8.4% vs. 80% ± 8.9%, P = 0.01) compared with patients without MAGEA expression. Conclusions The expression of MAGEA increased in osteosarcoma , which inversely correlating with outcome of osteosarcoma patients.
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Objective To detect the expression of SSX and to correlate it with clinical indicators of primary hepatocellular carcinoma (HCC).Methods The expression of SSX1-5 mRNA and SSX1 protein were respectively detected by RT-PCR and Western blot and immunohistochemistry staining.The relation between the expression of SSX mRNA and SSX1 protein with clinical indicators were analysed.Results SSX1,SSX2,and SSX3 mRNA were expressed in hepatocellular carcinoma cell lines BEL-7404,Hep G2,and SMMC-7721.In 26 HCC samples,SSX1-SSX5 mRNA was detectable in 53.8％,42.3％,50.0％,46.2％ and 26.9％.The expression of SSX1 mRNA was not related to serum AFP levels (P ＞0.05).Specific expression was both found in the normal group and the high value group.The expression rate of SSX1 mRNA was 85.7％ in the older group,which was higher than in the younger group (16.7％,P ＜ 0.05).The expression rate of SSX1 protein was 50％ in HCC tissues,which was not seen in the caner-adjacent or cirrhosis tissues.In 49 HCC paraffin tissue section samples,the expression rate of SSX1 protein was higher than that in caner-adjacent tissues (46.9％ vs 18.4％,P ＜ 0.05).The expression rate of SSX1 protein was 68.3％ in the large hepatocellular carcinoma group,which was higher than in the small hepatocellular carcinoma group (29.6％),(P ＜ 0.05).Conclusions SSX1 mRNA is expressed with a high percentage and specificity in HCC and their products are new potential promising targets for antigen-specific immunotherapy of HCC.The detection of SSX1 expression has the potential value for auxiliary diagnosis of HCC.
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BackgroundThe immunotherapy for retinoblastoma(RB) is gradually concerned recent year.To seek relative immune-associated antigen is a basis of immunotherapy.NY-ESO-1 and NY-SAR-35 are two kinds of genes of cancer testis antigen( CTA ).To understand their expressions in RB tissue can offer index for relative study.ObjectiveThis study was to investigate the expressions of two CTA NY-ESO-1 and NY-SAR-35 in RB and explore the possibility of them as potentially promising targets for antigen-specific immunotherapy of RB.Methods The samples were obtained from 15 RB eyes,12 non-tumor retinopathy eyes and 22 normal eyes with other benign eye diseases.Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expressions of NY-ESO-1 mRNA and NY-SAR-35 mRNA in the samples.Genes of positive PCR results were sequenced randomly.The relevance of the expression of the two cancer-testis antigen genes with the clinical characteristics such as tumor stage,tumor size and clinical stage were analyzed.This study was approved by Ethic Committee of Guangxi Medical University.Written informed consent was obtained from each patient before operation. Results NY-ESO-1 mRNA was positively expressed in 6 RB samples and NY-SAR-35 mRNA was expressed in 9 RB samples.In the non-tumor retinopathy samples and normal eye tissues,NY-ESO-1 mRNA and NY-SAR-35 mRNA were absent.No significant relevances were found between the expressions of the NY-ESO-1 mRNA and NY-SAR-35 mRNA with clinical characteristics such as age ( P =0.426,0.822 ),gender ( P =0.180,0.464 ),pathological classification ( P =0.744,0.582 ),tumor size ( P =0.760,0.790),and clinical stage ( P =0.868,0.707 ).Conclusions NY-ESO-1 and NY-SAR-35 have high expressing frequencies in RB tissue and their expressions in RB have specificity.These results offer a clue for the identification of targets antigen of RB.
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Os antígenos cancer-testis (CT) são proteínas imunogênicas expressas em tecido gametogênico e em diferentes tipos de tumor, sendo considerados candidatos promissores para a imunoterapia do câncer. Entretanto, pouco se sabe sobre a função desses antígenos na tumorigênese. Em 2006, identificamos CTSP-1 como um novo antígeno CT, frequentemente expresso em vários tumores. Nesse trabalho, investigamos a função de CTSP-1 por meio da identificação de proteínas expressas em tumores de próstata e que são capazes de interagir fisicamente com esse antígeno. Demonstramos que CTSP-1 interage com a proteína CTCF em ensaios de duplo-híbrido em leveduras, pulldown e de co-localização e, em seguida, analisamos o impacto da superexpressão de CTSP-1 no controle da expressão de genes CT mediada por CTCF e na progressão do ciclo celular. Utilizando o CT NY-ESO-1 como modelo, demonstramos que a superexpressão de CTSP-1 não altera os níveis endógenos de NY-ESO-1 na linhagem celular tumoral H1299. Por outro lado, observamos que a superexpressão de CTSP-1 48h após as transfecções em H1299 induz um bloqueio do ciclo em G0/G1, reduzindo a capacidade clonogênica dessas células por um mecanismo dependente dos níveis de expressão de CTSP-1. Resultados semelhantes não foram observados em ensaios com clones superexpressando CTSP-1 estavelmente, o que sugere que eles tenham se originado de células que conseguiram escapar do bloqueio em G0/G1. Resultados preliminares sugerem que a redução da capacidade clonogênica das células H1299 que superexpressam CTSP-1 48h após as tansfecções não está associada à ocorrência de morte por apoptose.
Cancer-testis (CT) antigens are immunogenic proteins expressed in gametogenic tissues and in different histological types of tumors, being considered promising candidates for cancer immunotherapy. However, little is known about their role in tumorigenesis. In 2006, we identified CTSP-1 as a novel CT antigen, frequently expressed in different types of tumors. In this work, we investigated the functional role of CTSP-1 through the identification of proteins expressed in prostate tumors and that physically interact with this tumor antigen. We demonstrate that CTSP-1 interacts with the CTCF protein using the yeast two-hybrid system, pulldown and co-localization assays and have further analyzed the impact of CTSP-1 overexpression on the expression of CT genes mediated by CTCF and on the cell cycle progression. Using the CT antigen NY-ESO-1 as a model, we showed that the CTSP-1 overexpression does not alter the endogenous levels of NY-ESO-1 in the tumor cell line H1299. On the other hand, we observed that the overexpression of CTSP-1 in H1299 cells 48h after the transfections induces a cell cycle arrest in G0/G1 and reduces the clonogenic capacity of these cells by a mechanism dependent on the CTSP-1 expression levels. Similar results were not observed for cell clones stably overexpressing CTSP-1, suggesting that these clones have arisen from cells that managed to escape cell cycle arrest in G0/G1. Preliminary results suggest that the reduced clonogenic capacity of H1299 cells expressing CTSP-1 and analyzed 48h after the transfections is not associated with cell death by apoptosis.
Assuntos
Ciclo Celular/genética , Biologia Molecular , Neoplasias da Próstata/imunologia , Mapeamento de Interação de Proteínas , Antígenos de Neoplasias/química , Células Neoplásicas Circulantes , Análise de Sequência de ProteínaRESUMO
Os antígenos cancer-testis (CT) são proteínas imunogênicas expressas em tecido gametogênico e em diferentes tipos de tumor, sendo considerados candidatos promissores para a imunoterapia do câncer. Entretanto, pouco se sabe sobre a função desses antígenos na tumorigênese. Em 2006, identificamos CTSP-1 como um novo antígeno CT, frequentemente expresso em vários tumores. Nesse trabalho, investigamos a função de CTSP-1 por meio da identificação de proteínas expressas em tumores de próstata e que são capazes de interagir fisicamente com esse antígeno. Demonstramos que CTSP-1 interage com a proteína CTCF em ensaios de duplo-híbrido em leveduras, pulldown e de co-localização e, em seguida, analisamos o impacto da superexpressão de CTSP-1 no controle da expressão de genes CT mediada por CTCF e na progressão do ciclo celular. Utilizando o CT NY-ESO-1 como modelo, demonstramos que a superexpressão de CTSP-1 não altera os níveis endógenos de NY-ESO-1 na linhagem celular tumoral H1299. Por outro lado, observamos que a superexpressão de CTSP-1 48h após as transfecções em H1299 induz um bloqueio do ciclo em G0/G1, reduzindo a capacidade clonogênica dessas células por um mecanismo dependente dos níveis de expressão de CTSP-1. Resultados semelhantes não foram observados em ensaios com clones superexpressando CTSP-1 estavelmente, o que sugere que eles tenham se originado de células que conseguiram escapar do bloqueio em G0/G1. Resultados preliminares sugerem que a redução da capacidade clonogênica das células H1299 que superexpressam CTSP-1 48h após as tansfecções não está associada à ocorrência de morte por apoptose
Cancer-testis (CT) antigens are immunogenic proteins expressed in gametogenic tissues and in different histological types of tumors, being considered promising candidates for cancer immunotherapy. However, little is known about their role in tumorigenesis. In 2006, we identified CTSP-1 as a novel CT antigen, frequently expressed in different types of tumors. In this work, we investigated the functional role of CTSP-1 through the identification of proteins expressed in prostate tumors and that physically interact with this tumor antigen. We demonstrate that CTSP-1 interacts with the CTCF protein using the yeast two-hybrid system, pulldown and co-localization assays and have further analyzed the impact of CTSP-1 overexpression on the expression of CT genes mediated by CTCF and on the cell cycle progression. Using the CT antigen NY-ESO-1 as a model, we showed that the CTSP-1 overexpression does not alter the endogenous levels of NY-ESO-1 in the tumor cell line H1299. On the other hand, we observed that the overexpression of CTSP-1 in H1299 cells 48h after the transfections induces a cell cycle arrest in G0/G1 and reduces the clonogenic capacity of these cells by a mechanism dependent on the CTSP-1 expression levels. Similar results were not observed for cell clones stably overexpressing CTSP-1, suggesting that these clones have arisen from cells that managed to escape cell cycle arrest in G0/G1. Preliminary results suggest that the reduced clonogenic capacity of H1299 cells expressing CTSP-1 and analyzed 48h after the transfections is not associated with cell death by apoptosis