Clinical significance of cancer/testis antigens expression in patients with non-small cell lung cancer

Shigematsu, Yoshiki; Hanagiri, Takeshi; Shiota, Hironobu; Kuroda, Koji; Baba, Tetsuro; Mizukami, Makiko; So, Tetsuya; Ichiki, Yoshinobu; Yasuda, Manabu; Saito, Tomoko; Takenoyama, Mitsuhiro; Yasumoto, Kosei

doi:10.1016/j.lungcan.2009.05.010

Cited by 80 publications

(77 citation statements)

References 43 publications

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“…MAGE-A is a member of CTAs characteristic with restricted expression in germline cells and aberrant expression in a variety of cancers of disparate origins [18][19]. It is often coordinated [33] and related to aggressive cancer types [34][35] and poor clinical prognosis [36]. To this end, we put forward that MAGE-A may be an important contributor to EMT of TNBC.…”

Section: Discussionmentioning

confidence: 99%

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

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Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.59%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of β-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and β-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.

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Section: Discussionmentioning

confidence: 99%

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

neo

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“…Despite advances in diagnostic and therapeutic modalities against lung cancer, there has been little improvement in patient prognostic outcomes. A clinical study identified immunotherapy as a potentially favorable alternative approach to the treatment of lung cancer (2). A large number of tumor-associated antigens have been identified in various types of human cancer, including the cancer-testis (CT) antigens.…”

Section: Introductionmentioning

confidence: 99%

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

2015

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Abstract. The cancer-testis (CT) family of antigens are expressed in multiple types of malignant neoplasm and are silent in normal tissues, apart from the testis. Immunotherapy targeting CT antigens is a promising therapeutic strategy for treatment of solid tumors. One member of this family, melanoma-associated antigen A4 (MAGE-A4), has been demonstrated to be expressed in melanomas and lung cancer. Patients with tumors expressing the MAGE-A4 antigen exhibit specific cellular and humoral immune responses to the antigen, resulting in a favorable prognosis. Conversely, the expression of MAGE-A4 is associated with poor survival in lung cancer. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells, which are upregulated in the cancer microenvironment. Little is known regarding any potential correlation between the expression of MAGE-A4 antigens and the accumulation of MDSCs. The present study aimed to examine the association between circulating MDSC levels and MAGE-A4 expression in a mouse model of Lewis lung cancer. The expression of MAGE-A4 in tumor cells or tissues was evaluated using western blotting, while the percentage of MDSCs (CD11b + Gr-1 + ) in the blood was detected by flow cytometry. In addition, the suppressive capacity of MDSCs and the effectiveness of MDSC depletion were assessed in C57BL/6 tumor-bearing mice. MDSCs were demonstrated to upregulate MAGE-A4 expression via the phosphosphorylated-signal transducer and activator of transcription 3 705 pathway, while depletion of MDSCs decreased the tumor growth rate, prolonged median survival and enhanced the recognition of MAGE-A4 by CD8 + T cells. These findings indicated that immunotherapeutic strategies involving induction of cytotoxic T lymphocytes that target MAGE-A4, in combination with MDSC depletion, may be an effective approach to immunotherapy for cancer types with high expression of MAGE-A4.

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“…16 Similarly, in other tumor types, CTA expression has been linked to prognosis. 17,18 Prognostic implications of CTAs post therapy have not been systematically evaluated. Three expression patterns have been defined for CTAs: expression restricted to testis, restricted to testis and brain, and expression in other tissues but strong expression in testis (testis-selective) 19 .…”

Section: Introductionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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Clinical significance of cancer/testis antigens expression in patients with non-small cell lung cancer

Cited by 80 publications

References 43 publications

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

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