Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue.

PURPOSE: Among tumor antigens identified to date, cancer-testis (CT) antigens, which are coded by CT genes, are identified as a group of highly attractive targets for cancer vaccines. This study is the first to analyze the mRNA expression and possible correlation with pathologic characteristics of multiple CT genes in a large cohort of colorectal cancer (CRC) patients. EXPERIMENTAL DESIGN: The expression of 10 individual CT genes in 121 CRC and adjacent tissues were analyzed by RT-PCR method. The presence of autologous antibodies against NY-ESO-1 was examined in serum samples by ELISA. To confirm the protein expression, immunohistochemistry was done for detecting the NY-ESO-1 antigen in mRNA-positive CRC tissues. RESULTS: The CT genes were detected with various frequencies in CRC tissue, SCP-1, 1.7%; SSX-2, 2.5%; SSX-4, 2.5%; SSX-1, 5.0%; CT10, 6.6%; NY-ESO-1, 9.9%; MAGE-1, 11.6%; LAGE-1, 15.7%; MAGE-4, 22.3%; and MAGE-3, 27.3%. In 56.2% of tumor tissues examined in this study, at least one CT gene was detected. In contrast, no CT gene expression was found in cancer adjacent tissues. Among 10 CT genes investigated, NY-ESO-1 and LAGE-1 are of particular interest because their mRNA expression in CRC was rarely reported before. In our study, NY-ESO-1 mRNA was found to express in 9.9% of the samples, and also correlated significantly with stages (P = 0.041) and local lymph node metastasis (P = 0.002). In addition, we also identified one NY-ESO-1 antibody-positive serum sample. MAGE-4 mRNA was expressed at a high frequency in tumor tissues with vessel emboli samples (P = 0.025). CONCLUSIONS: These results suggested that CT genes, especially NY-ESO-1 and LAGE-1, do express in CRC. More than 50% of the CRC patients in this study express at least one CT gene, making them eligible for CT vaccination. NY-ESO-1 gene may serve as a marker for local metastasis and advanced disease. MAGE-4 gene is significantly associated with the vessel emboli.

[Expression of NY-ESO-1/LAGE-1 genes in hepatocellular carcinoma and autologous humoral responses induced thereby].

OBJECTIVE: To investigate the potential of utilizing NY-ESO-1/LAGE-1 antigens in hepatocellular carcinoma (HCC) vaccines. METHODS: RT-PCR method was used to detect the expression of NY-ESO-1/LAGE-1 mRNA in the cancerous tissues and adjacent tissues resected from 34 patients with HCC. ELISA assay was adopted to analyze the NY-ESO-1 specific antibodies in 37 serum samples of HCC patients, 1 positive control sample, and 8 samples of normal persons. RESULTS: Nine (26.5%) out of the 34 HCC samples were NY-ESO-1 mRNA positive, while 12 (35.3%) were LAGE-1 positive. Among them, seven HCC samples expressed both genes, and 14 (41.6%) expressed at least one of the genes. Among the 37 serum samples tested six contained high titer of anti-NY-ESO-1 antibodies. Five of the samples were from stage III or later stage HCC patients; one was from a stage II patient. CONCLUSION: NY-ESO-1/LAGE-1 mRNA is expressed in a high frequency in HCC tissue samples, and induces autologous humoral responses in HCC patients. Both of the antigens can be considered as candidates for HCC vaccines.

[Expression of multiple cancer-testis antigen genes in non-small cell lung cancer treated by chemotherapy prior surgery].

OBJECTIVE: To investigate the possibility of utilizing cancer-testi (CT) antigens as targets for immunotherapy of non-small cell lung cancer (NSCLC) with vaccines. METHODS: Tissues from 51 NSCLC patients who had chemotherapy prior surgery were assayed for the expression of 11 different CT antigens by RT-PCR. RESULTS: Of the 11 CT antigens analyzed, MAGE-3 was found to be expressed most frequently in NSCLC tissues and CT7 the least frequently. The frequencies of CT antigen expression was: MAGE-3 (38%), NY-ESO-1 (21%), CT10 (17%), LAGE-1 (15%), MAGE-4 (13%), SCP-1, SSX1 and SSX4 (12%), MAGE-1 (10%), SSX2 (6%), and CT7 (2%). Among these cases, 34 (67%) expressed at least one CT antigen gene. 13 of the 17 cases in which no CT antigen expression was found in the tumor tissue, the tumors were classified as at the stage I. MAGE-3 and CT10 were found to be expressed more frequently in tissues from patients with late stage diseases while SCP-1 was found more frequently in earlier stages of NSCLC. CT expression was more frequently found in squamous cell carcinoma than in adenocarcinoma. CONCLUSIONS: (1) Cancer vaccines with CT antigens including MAGE-3, NY-ESO-1, LAGE-1, etc, are suitable for immunotherapy of NSCLC after chemotherapy and surgery. (2) NSCLC patients at different stages of disease may be treated with vaccines of different CT antigen composition. (3) CT antigen vaccines are most attractive for patients with late stage NSCLC and/or squamous cell carcinoma of NSCLC.

Dominant B cell epitope from NY-ESO-1 recognized by sera from a wide spectrum of cancer patients: implications as a potential biomarker.

Monitoring the spontaneous antibody (Ab) response against a panel of relevant tumor-associated antigens (TAA) in cancer patients may provide useful information regarding the clinical status of cancer. However, current Ab detection approaches require the purification of recombinant proteins, which is often difficult to achieve. In order to bypass the purification of recombinant proteins, we identified a dominant B-cell epitope from a shared tumor antigen NY-ESO-1. A synthetic peptide of the epitope, ESO:1-40, was as sensitive as the recombinant protein for detecting Ab against NY-ESO-1 in most patients. NY-ESO-1 specific Ab present in the sera of patients with melanoma, prostate cancer, nonsmall cell lung cancer, esophageal cancer, gastric cancer and hepatocellular carcinoma reacted with the dominant peptide at a similar frequency as the recombinant protein. To our knowledge, ESO:1-40 is the first peptide epitope recognized by sera from a wide spectrum of cancer patients but not healthy donors. This simple and straightforward approach may allow the investigation of the clinical significance of spontaneous Ab responses against multiple TAA and their correlation with the clinical course of malignant diseases in the future.