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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 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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Objective To explore the effects and the underlying mechanisms of inhibiting three kinds of DNA methyltransferases(DNMT1,DNMT3a and DNMT3b) on the re-expression of cancer/testis antigen(CTA) in hepatic cells.Methods Transient transfection of HepG2 cells with siRNA was targeted against DNMT1,DNMT3a and DNMT3b(DNMT1+3a+3b),DNMT1 and DNMT3a(DNMT1+3a),DNMT1 and DNMT3b(DNMT1+3b),DNMT3a and DNMT3b(DNMT3a+3b),respectively.The other batch of cells was treated with 5'-aza-deoxycytidine(5-aza-dC) as positive control.Real-time PCR and Western blotting were used to detect the expressions of DNMTs and CTAsm,and the promoter methylation of partial CTA genes was detected with methylation specific PCR(MSP).Results Expressions of DNMT1,DNMT3a and DNMT3b declined significantly after siRNA interference in HepG2 cells.Two CTAs,CT10 and SSX1,re-expressed in the cells transfected by DNMT1+3a and DNMT1+3b.MAGE1 and MAGE3 were equally expressed in all cells despite been transfected or not.Demethylation occurred in the promoter region of CT10,while the promoter region of MAGE1 was in a state of unmethylation.Conclusions In HepG2 cells,CTA promoter can be demethylated via interference of DNMTs,which may lead to the re-expression of CTA that was originally unexpressed due to methylation.