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Updated: Jan 22, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Systematic cancer-testis gene expression analysis identified CDCA5 as a potential therapeutic target in esophageal
Jing Xu1, Chengxiang Zhu1, Yue Yu2
1Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with poor prognosis. Cancer-testis genes (CTGs) have been vigorously pursued as targets for cancer immunotherapy, but the expressive patterns and functional roles of CTGs remain unclear in ESCC.
Methods:
A systematic screening strategy was adopted to screen CTGs in ESCC by integrating multiple public databases and RNA expression microarray data from 119 ESCC subjects. For the newly identified ESCC prognosis-associated CTGs, an independent cohort of 118 patients with ESCC was recruited to validate the relationship via immunohistochemistry. Furthermore, functional assays were performed to determine the underlying mechanisms.
Findings:
21 genes were recognized as CTGs, in particular, CDCA5 was aberrantly upregulated in ESCC tissues and significantly associated with poor prognosis (HR = 1.85, 95%CI: 1.14-3.01, P = .013). Immunohistochemical staining confirmed that positive CDCA5 expression was associated with advanced TNM staging and a shorter overall survival rate (45.59% vs 28.00% for CDCA5-/+ subjects, P = 1.86 × 10-3). H3K27 acetylation in CDCA5 promoter might lead to the activation of CDCA5 during ESCC tumorigenesis. Functionally, in vitro assay of gain- and loss-of-function of CDCA5 suggested that CDCA5 could promote ESCC cells proliferation, invasion, migration, apoptosis resistance and reduce chemosensitivity to cisplatin. Moreover, in vivo assay showed that silenced CDCA5 could inhibit tumor growth. Mechanistically, CDCA5 knockdown led to an arrest in G2/M phase and changes in the expression of factors that played fundamental roles in the cell cycle pathway.
Interpretation:
CDCA5 contributed to ESCC progression and might serve as an attractive target for ESCC immunotherapy. FUND: This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20181083 and BK20181496), Jiangsu Top Expert Program in Six Professions (No. WSW-003 and WSW-007), Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2016790 and BE2018746), Jiangsu Medical Young Talent Project (No. QNRC2016566), the Program of Jiangsu Medical Innovation Team (No. CXTDA2017006), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1487) and Jiangsu Province 333 Talents Project (No. BRA2017545).
Insights
Cell division cycle associated 5 (CDCA5) promotes esophageal squamous cell carcinoma (ESCC) progression and may be a target for immunotherapy. Silencing CDCA5 inhibits tumor growth and improves chemosensitivity in ESCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Esophageal squamous cell carcinoma (ESCC) is a lethal cancer with poor prognosis.
- Cancer-testis genes (CTGs) are investigated for cancer immunotherapy, but their roles in ESCC are not fully understood.
Purpose of the Study:
- To screen for and characterize cancer-testis genes (CTGs) associated with prognosis in esophageal squamous cell carcinoma (ESCC).
- To investigate the functional role and underlying mechanisms of CDCA5 in ESCC progression and its potential as an immunotherapy target.
Main Methods:
- Systematic screening of CTGs using public databases and RNA expression data from 119 ESCC patients.
- Validation of prognosis-associated CTGs in an independent cohort of 118 ESCC patients via immunohistochemistry.
- Functional assays (in vitro and in vivo) and mechanistic studies to assess CDCA5's role in ESCC.
Main Results:
- 21 CTGs were identified; CDCA5 was significantly upregulated in ESCC and associated with poor prognosis (HR=1.85).
- Positive CDCA5 expression correlated with advanced TNM staging and shorter survival (P < .002).
- CDCA5 promoted ESCC cell proliferation, invasion, migration, apoptosis resistance, and cisplatin resistance, while its silencing inhibited tumor growth and caused G2/M cell cycle arrest.
Conclusions:
- CDCA5 contributes to ESCC progression and represents a potential therapeutic target for ESCC immunotherapy.
- Targeting CDCA5 may offer a novel strategy for improving treatment outcomes in esophageal squamous cell carcinoma.
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