MAGE-A family expression is correlated with poor survival of patients with lung adenocarcinoma: a retrospective clinical study based on tissue microarray

Sang, Meixiang; Gu, Lina; Yin, Danlei; Liu, Fei; Lian, Yishui; Zhang, Xiaochong; Liu, Shina; Huang, Weina; Wu, Yunyan; Shan, Baoen

doi:10.1136/jclinpath-2016-203718

Cited by 29 publications

(17 citation statements)

References 36 publications

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“…The survival analysis revealed that a high level of MAGE-A1 expression was correlated with unfavorable outcomes of LUAD. All the above data concurred with the studies that showed high expression levels and a prognostic role of MAGE-A1 in LUAD [43, 45, 46].…”

Section: Discussionsupporting

confidence: 90%

“…As a member of the MAGE-A antigens, which are the best characterized CTAs, MAGE-A1 is also strictly tumor-specific and is detected in various solid tumors [40–42]. Although MAGE-A1 expression in LC has also been reported [43–45], the detailed and exclusive function of MAGE-A1 in LUAD remains unclear. After MAGE-A1 was screened as the most promising candidate by the aforementioned bioinformatics analyses, a set of investigations was performed to thoroughly examine the characteristics of MAGE-A1 in LUAD.…”

Section: Discussionmentioning

confidence: 99%

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MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells

Yuan

Fan

et al. 2019

J Hematol Oncol

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BackgroundCancer/testis antigens (CTAs) are a special type of tumor antigen and are believed to act as potential targets for cancer immunotherapy.MethodsIn this study, we first screened a rational CTA MAGE-A1 for lung adenocarcinoma (LUAD) and explored the detailed characteristics of MAGE-A1 in LUAD development through a series of phenotypic experiments. Then, we developed a novel MAGE-A1-CAR-T cell (mCART) using lentiviral vector based on our previous MAGE-A1-scFv. The anti-tumor effects of this mCART were finally investigated in vitro and in vivo.ResultsThe results showed striking malignant behaviors of MAGE-A1 in LUAD development, which further validated the rationality of MAGE-A1 as an appropriate target for LUAD treatment. Then, the innovative mCART was successfully constructed, and mCART displayed encouraging tumor-inhibitory efficacy in LUAD cells and xenografts.ConclusionsTaken together, our data suggest that MAGE-A1 is a promising candidate marker for LUAD therapy and the MAGE-A1-specific CAR-T cell immunotherapy may be an effective strategy for the treatment of MAGE-A1-positive LUAD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells

Yuan

Fan

et al. 2019

J Hematol Oncol

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“…For instance, miR-34a has been reported to regulate carcinogenesis by targeting several mRNAs, including MAGE-A in medulloblastoma (22), programmed cell death 1 ligand 1 or lactate dehydrogenase A in breast cancer (28), and B cell lymphoma-2 in cervical cancer (29). The expression of MAGE-A has been documented to be upregulated in gastric cancer (35), epithelial ovarian cancer (36), and lung adenocarcinoma tissues and cells (37). In agreement with the aforementioned studies, the results of the RT-qPCR analysis in the present study revealed that the mRNA level of MAGE-A was significantly upregulated in RB tissues compared with paracarcinoma tissues (P<0.05).…”

Section: Discussionmentioning

confidence: 99%

miR‑34a regulates the chemosensitivity of retinoblastoma cells via modulation of MAGE‑A/p53 signaling

Yang

et al. 2018

Int J Oncol

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The present study aimed to explore the combined role of microRNA (miR)-34a, melanoma antigen-A (MAGE-A) and p53 in altering the chemosensitivity of retinoblastoma (RB) cells. Human RB and adjacent tumor tissues, as well as human RB cell lines (HXO-Rb44, SO-Rb50, Y79 and WERI-Rb-1) were used. In addition, four chemotherapeutic drugs, including carboplatin, etoposide, Adriamycin and vincristine, were used to treat the cell lines, in order to evaluate the sensitivity of RB cells. Furthermore, miR-34a expression was detected by reverse transcription-quantitative polymerase chain reaction, and western blotting was implemented to quantify expression levels of MAGE-A and p53. A luciferase reporter gene assay was used to validate the targeted association between miR-34a and MAGE-A. The results indicated that SO-Rb50 cells exhibited the highest resistance to carboplatin, Adriamycin and vincristine (P<0.05), whereas HXO-Rb44 cells revealed the highest inhibition rate in response to etoposide (P<0.05) out of the four cell lines. Furthermore, reduced miR-34a expression and increased MAGE-A expression significantly elevated the survival rate and viability of SO-Rb50 cells following drug treatment (all P<0.05). miR-34a was also demonstrated to directly target MAGE-A, thereby significantly promoting the viability of RB cells and depressing apoptosis (P<0.05). p53, which was subjected to modulation by miR-34a and MAGE-A, also significantly reduced the proliferation rate of RB cells (P<0.05). In conclusion, the miR-34a/MAGE-A/p53 axis may be conducive to enhancing the efficacies of chemotherapeutic treatments for RB.

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“…TMAs construction, HE and IHC staining were performed and analyzed as described in our previous study [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

MAGE-A11 is activated through TFCP2/ZEB1 binding sites de-methylation as well as histone modification and facilitates ESCC tumor growth

Liu

Huang

et al. 2017

Oncotarget

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Recently, we have reported that the product of Melanoma Antigens Genes (MAGE) family member MAGE-A11 is an independent poor prognostic marker for esophageal squamous cell carcinoma (ESCC). However, the reason how MAGE-A11 is activated in ESCC progression still remains unclear. In the current study, we demonstrated that DNA methylation and the subsequent histone posttranslational modifications play crucial roles in the regulation of MAGE-A11 in ESCC progression. We found that the methylation rate of TFCP2/ZEB1 binding site on MAGE-A11 promoter in ESCC tissues and cells is higher than the normal esophageal epithelial tissues and cells. Transcription factors TFCP2 and ZEB1 directly bind MAGE-A11 promoter and regulate the endogenous MAGE-A11 expression in a methylation-dependent manner in ESCC cells. Following MAGE-A11 promoter methylation, the methyl-CpG-binding protein MeCP2 was found to bind the methylated MAGE-A11 promoter to mediate histone deactylation by recruiting HDAC1 and HDAC2. Simultaneously, histone inactivation marks including H3K27me3 as well as H3K9me3 were increased, whereas histone activation mark H3K4me3 was decreased. HDAC inhibitor Trichostatin A (TSA) increased DNA methylase inhibitor Decitabine (DAC)-induced MAGE-A11 expression. siRNA-mediated knockdown of histone methltransferase EZH2 or DZNep (a EZH2 inhibitor) treatment increased DAC-induced MAGE-A11 expression. Our results indicate that MAGE-A11 is activated through DNA demethylation, histone acetylation and histone methylation in ESCC, and its activation promotes ESCC tumor growth.

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MAGE-A family expression is correlated with poor survival of patients with lung adenocarcinoma: a retrospective clinical study based on tissue microarray

Abstract: Molecular assessment of MAGE-A family members could be considered to improve the prognostic evaluation and to provide a new potential therapeutic strategy for patients with LAC.

Cited by 29 publications

References 36 publications

MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells

MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells

miR‑34a regulates the chemosensitivity of retinoblastoma cells via modulation of MAGE‑A/p53 signaling

MAGE-A11 is activated through TFCP2/ZEB1 binding sites de-methylation as well as histone modification and facilitates ESCC tumor growth

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