The relationship between NY-ESO-1 mRNA expression and clinicopathological features in non-small cell lung cancer

Konishi, Juichiro; Toyooka, Shinichi; Aoe, Motoi; Omura, Yasushi; Washio, Kazuhiro; Tsukuda, Kazunori; Shimizu, Nobuyoshi

doi:10.3892/or.11.5.1063

Cited by 14 publications

(14 citation statements)

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“…Vaccines using either CD4-or CD8-restricted peptide epitopes, or full-length recombinant NY-ESO-1 protein have enhanced anti-NY-ESO-1 reactivity in cancer patients, some of whom have exhibited disease regression following immunization (36,37). Whereas nearly 30% of non-small cell lung cancer and 75% of small cell lung cancer (SCLC) express NY-ESO-1 (38,39), immune response to this CTA seems limited in lung cancer patients (40). Although this apparent lack of immune response to NY-ESO-1 may be attributable, at least in part, to deficiencies regarding antigen processing/presentation, particularly in SCLC (41,42), and the immunosuppressive effects of regulatory T cells, which are abundant within the primary tumors as well as the systemic circulation of lung cancer patients (43,44), in many instances, levels of NY-ESO-1 expression in primary lung carcinomas may simply be below the threshold for immune recognition.…”

Section: Resultsmentioning

confidence: 99%

Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells

et al. 2005

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Regulatory sequences recognized by the unique pair of paralogous factors, CTCF and BORIS, have been implicated in epigenetic regulation of imprinting and X chromosome inactivation. Lung cancers exhibit genome-wide demethylation associated with derepression of a specific class of genes encoding cancer-testis (CT) antigens such as NY-ESO-1. CT genes are normally expressed in BORIS-positive male germ cells deficient in CTCF and meCpG contents, but are strictly silenced in somatic cells. The present study was undertaken to ascertain if aberrant activation of BORIS contributes to derepression of NY-ESO-1 during pulmonary carcinogenesis. Preliminary experiments indicated that NY-ESO-1 expression coincided with derepression of BORIS in cultured lung cancer cells. Quantitative reverse transcription-PCR analysis revealed robust, coincident induction of BORIS and NY-ESO-1 expression in lung cancer cells, but not normal human bronchial epithelial cells following 5-aza-2V -deoxycytidine (5-azadC), Depsipeptide FK228 (DP), or sequential 5-azadC/DP exposure under clinically relevant conditions. Bisulfite sequencing, methylation-specific PCR, and chromatin immunoprecipitation (ChIP) experiments showed that induction of BORIS coincided with direct modulation of chromatin structure within a CpG island in the 5V -flanking noncoding region of this gene. Cotransfection experiments using promoter-reporter constructs confirmed that BORIS modulates NY-ESO-1 expression in lung cancer cells. Gel shift and ChIP experiments revealed a novel CTCF/BORIS-binding site in the NY-ESO-1 promoter, which unlike such sites in the H19-imprinting control region and X chromosome, is insensitive to CpG methylation in vitro. In vivo occupancy of this site by CTCF was associated with silencing of the NY-ESO-1 promoter, whereas switching from CTCF to BORIS occupancy coincided with derepression of NY-ESO-1. Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas. (Cancer Res 2005; 65(17): 7763-74)

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Section: Resultsmentioning

confidence: 99%

Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells

et al. 2005

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“…For example, the expression of NY-ESO-1 protein has been reported to be correlated with the metastasis of HCC (12). In non-small cell lung cancer, NY-ESO-1 expression significantly increased with the advancement of disease stage in the TNM classification, particularly that related to lymph node metastasis (19). In addition, NY-ESO-1 is more frequently expressed in metastatic than in primary malignant melanoma and its expression is associated with advanced stage (20).…”

Section: Discussionmentioning

confidence: 99%

NY-ESO-1 expression in hepatocellular carcinoma: A potential new marker for early recurrence after surgery

Liu

et al. 2011

Oncology Letters

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Abstract. NY-ESO-1 belongs to the cancer testis antigens (CTA) family, and is identified in a variety of tumors. Certain studies have demonstrated that NY-ESO-1 predicts tumor recurrence and treatment response. No reports are currently available regarding the correlation between NY-ESO-1 and the recurrence of hepatocellular carcinoma (HCC) following surgery. The purpose of the present study was to evaluate the association between NY-ESO-1 and relapse of HCC and to explore the possible mechanisms for this correlation. A total of 120 HCC patients were analyzed for the expression of NY-ESO-1 by immunohistochemistry (IHC). A stable NY-ESO-1 over-expressed HepG2 cell line (ESO-HepG2) was established to determine the biological effects of NY-ESO-1 on cell proliferation, cell cycle and migration by using the xCELLigence DP system, flow cytometry and xCELLigence SP system. NY-ESO-1 was positive in 28 of 120 (23.3%) HCC tumor tissues. NY-ESO-1 was not detectable in adjacent normal liver tissues. A close correlation was found between NY-ESO-1 expression and the recurrence of HCC following surgery (P= 0.007). Kaplan-Meier analysis showed a shorter recurrence-free survival (RFS) for patients positive for NY-ESO-1 (log-rank test, P=0.003). The Cox regression model demonstrated that NY-ESO-1 expression was a significant independent predictor for the recurrence of HCC following curative surgery (P= 0.022). Compared with HepG2 cells, ESO-HepG2 cells have increased migration but not proliferation ability. In conclusion, NY-ESO-1 expression is associated with worse HCC outcome following surgery, and the mechanism for this finding may be that NY-ESO-1 increases tumor cell migration. IntroductionHepatocellular carcinoma (HCC) is the fifth most common cancer in the world and one of the most prevalent malignancies in Asia (1). Current curative treatment options include surgical resection and liver transplantation. Liver transplantation is effective only in the early stages of disease. Surgery is possible in few patients and curative in only a small percentage, due to recurrence following the surgery (2). Besides exploring effective therapeutic methods, investigators are attempting to find biomarkers to predict tumor recurrence. The NY-ESO-1 antigen was originally found in esophageal cancer by serological recombinant cDNA expression cloning (SEREX) and belongs to the cancer/testis antigen (CTA) family (3). NY-ESO-1 expression is restricted to testicular germ cells in normal adult tissues and is found in numerous malignancies including malignant melanoma, hepatoma, breast and lung cancer. The NY-ESO-1 protein is known to be markedly immunogenic for numerous advanced and metastatic types of cancer (4,5). NY-ESO-1 is a potential biomarker for the prediction of tumor recurrence and treatment outcomes in a variety of tumors, including gastrointestinal stromal tumors (6) and cutaneous melanoma (7).Although a number of studies showed inconsistently that NY-ESO-1 is positive in certain HCCs (8-16), two studies have demonstrated that NY-ESO-1 ...

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“…Vaccines using either CD4 or CD8 T-cell-restricted peptide epitopes, or fulllength recombinant NY-ESO-1 protein, have enhanced anti-ESO-1 reactivity in cancer patients, some of whom have exhibited disease regression following immunization (47,48). Whereas NY-ESO-1 is frequently expressed in pulmonary carcinomas (23,49), immune De novo Induction of a Tumor Antigen for Immunotherapy www.aacrjournals.org response to this CTA seems limited in lung cancer patients (21). Nevertheless, our experience concerning induction of NY-ESO-1 in tumor tissues from lung cancer patients, and detection of NY-ESO-1 antibodies in several of these individuals following exposure to chromatin remodeling agents, 6 attests to the potential utility of gene induction regimens for enhancing the immunogenicity of lung cancer cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

De novoInduction of a Cancer/Testis Antigen by 5-Aza-2′-Deoxycytidine Augments Adoptive Immunotherapy in a Murine Tumor Model

Hong²,

et al. 2006

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Recent studies suggest that immunotherapy targeting specific tumor-associated antigens (TAAs) may be beneficial in cancer patients. However, most of these TAAs are tumor type specific and heterogeneous among patients, thus limiting their applications. Here, we describe the de novo induction of a cancer/testis antigen (CTA) for immunotherapy of tumors of various histologies. The murine CTA P1A, normally expressed only in a few tumor lines, could be induced de novo in all P1A-negative cancer lines of eight histologic origins in vitro and in various murine xenografts by systemic administration of 5-aza-2V -deoxycytidine. The induction of P1A expression correlated strongly with demethylation of the CpG island in the promoter region of this gene. The induced antigen was processed and presented properly for recognition by H-2L drestricted P1A-specific CTLs. The combination of a demethylating agent and adoptive transfer of P1A-specific CTL effectively treated lung metastases in syngeneic mice challenged with P1A-negative 4T1 mammary carcinoma cells. These data show a novel strategy of combined chemoimmunotherapy of cancer targeting a CTA induced de novo in a broad range of tumor histologies, and support further evaluation of chromatin-remodeling agents for human cancer therapy. (Cancer Res 2006; 66(2): 1105-13)

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The relationship between NY-ESO-1 mRNA expression and clinicopathological features in non-small cell lung cancer

Cited by 14 publications

References 0 publications

Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells

Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells

NY-ESO-1 expression in hepatocellular carcinoma: A potential new marker for early recurrence after surgery

De novoInduction of a Cancer/Testis Antigen by 5-Aza-2′-Deoxycytidine Augments Adoptive Immunotherapy in a Murine Tumor Model

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