Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non–Small Cell Lung Cancer

Gure, Ali Osmay; Chua, Ramon; Williamson, Barbara; Gönen, Mithat; Ferrera, Cathy A.; Gnjatic, Sacha; Ritter, Gerd; Simpson, Andrew J.G.; Chen, Yao-T.; Old, Lloyd J.; Altorki, Nasser K.

doi:10.1158/1078-0432.ccr-05-1203

Cited by 313 publications

(274 citation statements)

References 60 publications

(22 reference statements)

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“…This is in agreement with recent findings in other cancers showing that CT-X gene expression is often coordinated due to hypomethylation of their promoters (50,51). In addition, CT-X gene expression in patients with epithelial cancers is often associated with a poor patient outcome (52)(53)(54). Our data are also in agreement with recent studies emphasizing that the MMC of patients that express MAGE-C1, MAGE-A3, and/or NY-ESO-1 had an increased proliferative activity and are obtained mainly from patients with stage III MM (32,40).…”

Section: Discussionsupporting

confidence: 92%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

109

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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Section: Discussionsupporting

confidence: 92%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

109

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“…Third, the expression of CT45 in lung cancer varied in different histologic types, being less frequent in adenocarcinoma than in other types, e.g., SQCC. 28 Finally, by systematically comparing the CT45 mRNA and protein expressions in lung cancer and in ovarian cancer, we have found CT45 protein expression to correlate with the level of mRNA expression, and tumors that contain CT45 mRNA levels at <1% of testicular expression often do not express detectable levels of CT45 protein. This last observation is similar to the findings in NY-ESO-1 by us and other groups.…”

Section: Discussionmentioning

confidence: 88%

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Chen

Hsu

Lee

et al. 2009

Intl Journal of Cancer

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CT45 is a cancer/testis gene that we previously identified by massively parallel signature sequencing. Encoded by a multigene family on chromosome X, CT45 showed restricted mRNA expression to normal testis and various cancers. In this study, monoclonal antibodies were generated against recombinant CT45 protein, and CT45 protein expression in normal and tumor tissues was evaluated by immunohistochemical analysis. In adult normal tissue, CT45 expression was restricted to testicular germ cells, detected as a nuclear protein mainly at the stage of primary spermatocytes. In tumors, CT45 protein expression correlated with the mRNA levels detected by quantitative RT-PCR, and most lung cancer and ovarian cancers with CT45 mRNA at levels >1% of testicular expression were CT45 protein-positive. In positive cases, CT45 showed expression patterns that ranged from diffuse strong staining to heterogeneous and patchy expression. In lung cancer, CT45 expression was least frequent in adenocarcinoma, more frequent in squamous cell carcinoma and neuroendocrine tumors. Using tissue microarrays, 376 lung cancer, 219 ovarian cancer and 155 breast cancer were evaluated for CT45 protein expression. The expression frequency was highest in ovarian cancer (37%), followed by lung cancer (13%) and lowest in breast cancer (<5%). Given the focal nature of CT45 expression in many cases, these numbers represented the minimal frequency of expression in these tumor types. In summary, the expression frequency and characteristics of CT45 expression are similar to other CT cancer vaccine targets currently in clinical trials, e.g., NY-ESO-1 and MAGE-A, suggesting CT45 as a potentially useful cancer target. ' 2009 UICC

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“…The MAGE-A family of tumorspecific cancer-testis antigens includes 15 genes clustered on Xq28 (9). MAGE-A-encoded antigens are expressed in various cancers, including NSCLC (10)(11)(12). The frequency of MAGE-A expression, however, is variable among tumor types and subtypes (13); whereas expression of MAGE-A is known to be regulated through epigenetic mechanisms (14), the molecular factors that account for this variability remain undefined.…”

Section: Introductionmentioning

confidence: 99%

“…The frequency of MAGE-A expression, however, is variable among tumor types and subtypes (13); whereas expression of MAGE-A is known to be regulated through epigenetic mechanisms (14), the molecular factors that account for this variability remain undefined. The physiologic function of MAGE-A proteins and their role in cancer have not been elucidated, although there is increasing evidence that some MAGE-A proteins may correlate with poor clinical outcome (11,15). MAGE-A antigens, nonetheless, are immunogenic and are important targets of emerging immunotherapy approaches in NSCLC (16).…”

Section: Introductionmentioning

confidence: 99%

Assessment of MAGE-A Expression in Resected Non–Small Cell Lung Cancer in Relation to Clinicopathologic Features and Mutational Status of EGFR and KRAS

Ayyoub

Memeo

Álvarez-Fernández

et al. 2014

Cancer Immunology Research

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Non-small cell lung cancer (NSCLC) is a major public health problem, accounting for more cancer-related deaths than any other cancer. Both immunotherapy, based on the expression of tumor-specific antigens, and targeted therapy, based on the presence of oncogenic mutations, are under development for NSCLC. In this study, we analyzed the expression of MAGE-A, a cancer-testis antigen, in tumors from a cohort of patients with resected NSCLC with respect to their clinicopathologic characteristics and their mutational status for the EGFR and KRAS genes. We found MAGE-A expression by IHC in 43% of the tumors. MAGE-A expression was significantly more frequent in squamous tumors than in adenocarcinomas, did not correlate with disease stage, but was correlated significantly with high tumor grade and worse survival. EGFR and KRAS mutations were present in adenocarcinomas, but not in squamous tumors. Whereas the presence of EGFR mutations did not seem to affect survival, the presence of KRAS mutations was associated with early-stage disease and better survival. MAGE-A expression was absent from adenocarcinomas with KRAS mutations, but not significantly different in tumors with or without EGFR mutations. Together, the reported results provide guidance for the design of combination therapies in patients with NSCLC. Cancer Immunol Res; 2(10); 943-8. Ó2014 AACR.

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Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non–Small Cell Lung Cancer

Abstract: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.

Cited by 313 publications

References 60 publications

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Assessment of MAGE-A Expression in Resected Non–Small Cell Lung Cancer in Relation to Clinicopathologic Features and Mutational Status of EGFR and KRAS

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