Related Experiment Videos
SEREX analysis of gastric cancer antigens
Y Obata1, T Takahashi, J Sakamoto
1Aichi Cancer Center, Research Institute and Department of Genetics and Pathology, Aichi Cancer Center Hospital, Nagoya, Japan. yobata@aichi-cc.pref.aichi.jp
Abstract:
Stomach cancer is the major malignancy in Japan and one of the most common cancers worldwide. To establish the basis for an immunotherapeutic approach to stomach cancer, we have initiated an analysis of stomach cancer antigens recognized by human immunoglobulin G (IgG) antibodies using SE-REX, a powerful expression cloning method developed by Dr. M. Pfreundschuh's group. Five stomach cancer cDNA libraries have been screened with autologous patient sera: one moderately differentiated adenocarcinoma; two poorly differentiated adenocarcinomas; and two scirrhous-type poorly differentiated adenocarcinomas of Borrmann type 4, the most devastating form of stomach cancer. Based on the reactivities of clones with autologous IgG antibodies, an average of 50 independent clones from each library and a total of 297 clones were isolated. DNA sequencing revealed that these 297 clones were derived from 136 different genes. Comparison of the 136 genes to sequences in DNA databases showed that 95 are previously identified genes and 41 are newly identified in this study. The antigens are derived from various genes including a chimeric gene between E-cadherin and an unknown gene Y, AKT oncogene, genes overexpressed in stomach cancers, genes of which the transcripts are alternatively or aberrantly spliced, and genes known to be involved in autoimmune diseases. Thus stomach cancer patients can generate an immune response against a surprisingly diverse set of gene products. To identify antigens potentially useful in the diagnosis and therapy of gastric cancer, all 136 genes were tested for their reactivities with a panel of sera from 44 gastric cancer patients (17 women and 27 men, aged 35-81 years) and with a panel of sera from 100 control individuals with no previous history of cancer but some of whom had gastritis (55 women and 45 men, aged 30-69 years). Eleven antigens showed reactivity only with a certain proportion of cancer patient sera but not with any control sera. An additional 12 antigens elicited antibody production at a much higher frequency in cancer patients than in control individuals. To evaluate the clinical usefulness of these antigens we are now examining their expression in normal and malignant tissues.
Insights
Researchers identified diverse stomach cancer antigens recognized by patient antibodies. This discovery advances immunotherapies and diagnostics for this common malignancy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Stomach cancer is a leading malignancy in Japan and globally.
- Developing immunotherapeutic strategies requires understanding antigens recognized by patient antibodies.
Purpose of the Study:
- To identify novel stomach cancer antigens recognized by human immunoglobulin G (IgG) antibodies.
- To lay the groundwork for immunotherapeutic approaches to stomach cancer.
Main Methods:
- Screened five stomach cancer cDNA libraries using autologous patient sera.
- Utilized the SE-REX expression cloning method.
- Analyzed 297 isolated clones derived from 136 different genes.
Main Results:
- Identified 136 distinct genes encoding stomach cancer antigens, including 41 newly discovered genes.
- Eleven antigens showed specific reactivity with cancer patient sera, not control sera.
- Twelve additional antigens elicited significantly higher antibody responses in cancer patients.
Conclusions:
- Stomach cancer patients exhibit immune responses to a wide array of gene products.
- Identified antigens hold potential for diagnostic and therapeutic applications in gastric cancer.
- Further examination of antigen expression in normal and malignant tissues is ongoing.