Systematic cancer-testis gene expression analysis identified CDCA5 as a potential therapeutic target in esophageal squamous cell carcinoma

Abstract

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).

Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy

“… 46 Furthermore, several studies found that CT genes play fundamental roles in the cell cycle pathway in tumorigenesis. 20 , 47 In line with this, in our present analysis, CT gene in HCC was found mainly involves in the regulation of cell cycle, intriguingly both in mitotic and in meiotic, which is essential for tumorigenesis. This is consistent with the fact that CT gene is highly testicular and cancer-specific, making it a promising candidate molecular-targeted therapies for HCC.…”

“…Prognostic values of CT genes were reported in many tumor types, such as multiple myeloma, 53 clear cell renal cell carcinoma, 54 testicular germ cell tumor, 55 and esophageal squamous cell carcinoma. 47 In our study, survival analysis revealed that 9 CT genes of our identified hub CT genes were associated with the poor survival of HCC, which makes them promising candidate prognostic biomarkers for HCC. These findings lead to a possibility that these CT gene products might have a functional role in the pathogenesis of cancer resulting in a bad evolution.…”

Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods

“…In addition, it has also been con rmed that CDCA5 was signi cantly upregulated in breast cancer, bladder cancer, oral squamous cell cancer, urinary tract carcinoma, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma, and the high expression of CDCA5 was closely related to pathological stages and poor prognosis of patients [21][22][23][24][25][26].…”

Construct ion of co - expression modules related to survival by WGCNA and identif ication of potential prognostic biomarkers in glioblastoma

“…In order to explore the specific mechanism of the effect of these genes on survival, we screened the top 10 genes (CDC20, NCAPH, CDCA5, BUB1, CDCA8, PBK, KIF2C, TPX2, TTK and TOP2A). By retrieving related literature, we found that CDCA5 and CDCA8, as important regulatory proteins in the cell cycle in cancer, were recognized as oncogenes [26][27][28][29]. However, compared with other genes, there scarcely no reports about the mechanism of CDCA5 and CDCA8 with GBM.…”