Expression of Cancer-Testis Antigens MAGE-A1, MAGE-A4, NY-ESO-1 and PRAME in Bone and Soft Tissue Sarcomas: The Experience From a Single Center in China.

Anni Chen, Yuling Qiu, Ying-Tzu Yen, Chun Wang, Xiaolu Wang, Chunhua Li, Zijian Wei, Lin Li, Lixia Yu, Fangcen Liu, Rutian Li
Author Information
  1. Anni Chen: Nanjing University of Chinese Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  2. Yuling Qiu: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  3. Ying-Tzu Yen: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  4. Chun Wang: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  5. Xiaolu Wang: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  6. Chunhua Li: Nanjing University of Chinese Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  7. Zijian Wei: Nanjing University of Chinese Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  8. Lin Li: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  9. Lixia Yu: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
  10. Fangcen Liu: Nanjing University of Chinese Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  11. Rutian Li: Nanjing University of Chinese Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. ORCID

Abstract

OBJECTIVE: Sarcomas are a heterogeneous group of malignancies, low disease-control levels and the limited durability of responses have prompted the exploration of various novel immunotherapeutic approaches. To preliminarily explore the feasibility of cancer vaccines based on cancer testis antigen in the immunotherapy of sarcomas, we investigate the expression of Cancer/Testis Antigens (CTA) MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in bone and soft tissue sarcomas, with the aim of assessing their potential for use in sarcoma immunotherapy and determining their expression levels in different subtypes.
METHODS AND RESULTS: We employed immunohistochemistry and multiplex immunostaining microarrays (MI chips) to assess the expression of MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in 21 cases of undifferentiated pleomorphic sarcoma (UPS), 26 cases of smooth muscle sarcoma, 28 cases of liposarcoma, 40 cases of osteosarcoma (OS), and 13 cases of chondrosarcoma. MAGE-A1 showed the highest expression in osteosarcoma (32.50%), while it was lower in liposarcoma and undifferentiated pleomorphic sarcoma (10.71% and 10.00%) and undetectable in chondrosarcoma. MAGE-A4 expression was elevated in osteosarcoma and undifferentiated pleomorphic sarcoma (40.00% and 33.00%), but lower in liposarcoma and smooth muscle sarcoma (17.00% and 33.00%). NY-ESO-1 expression was relatively low across all sarcoma subtypes. PRAME expression was highest in undifferentiated pleomorphic sarcoma (47.62%) and low in chondrosarcoma (7.69%). None of the sarcomas expressed KK-LC-1. Additionally, while there was no statistically significant correlation between CTA expression and patient age or gender, some differences related to age and gender were observed.
CONCLUSIONS: CTA expression in bone and soft tissue sarcomas was correlated with both CTA type and sarcoma subtype, showing relatively high levels of expression in undifferentiated pleomorphic sarcoma (UPS) and osteosarcoma (OS). The poly-expression of MAGE-A4, PRAME, and MAGE-A1 across all subtypes suggests that these antigens may serve as potential targets for sarcoma-specific immunotherapy.

Keywords

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Grants

  1. YKK22086/Youth project of Nanjing Medical Science and Technology Development Fund
  2. 82203178/Project supported by the Young Scientists Fund of the National Natural Science Foundation of China
  3. BK20240017/Science Fund for Distinguished Young Scholars of Jiangsu Province
  4. BK20220191/The Youth Fund Project of Natural Science Foundation of Jiangsu Province Basic Research Program
  5. 82272852/National Natural Science Foundation of China
  6. 2022-LCYJ-PY-21/Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University

MeSH Term

Humans
Antigens, Neoplasm
Sarcoma
Male
Female
Membrane Proteins
Neoplasm Proteins
Bone Neoplasms
Adult
Middle Aged
China
Adolescent
Melanoma-Specific Antigens
Young Adult
Aged
Immunohistochemistry
Biomarkers, Tumor
Child
Soft Tissue Neoplasms

Chemicals

Antigens, Neoplasm
CTAG1B protein, human
PRAME protein, human
Membrane Proteins
Neoplasm Proteins
MAGEA4 protein, human
Melanoma-Specific Antigens
Biomarkers, Tumor
MAGEA1 protein, human

Word Cloud

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