Discover oncology · 2026
Integrated bioinformatics and in vitro validation reveal the role of CCT5 in immune infiltration and the Wnt pathway in colon cancer.
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Wang Bo, Liu Xinrui, Li Jianmei, Dong Hui, Fan Xingxiu, Wang Ruijun, Guo Jianping, Li Yifeng
Аннотация
OBJECTIVES: While Chaperonin Containing TCP1 Subunit 5 (CCT5) is recognized for its involvement in the oncogenesis and advancement of diverse malignancies, its functional significance within the context of colon adenocarcinoma (COAD) has yet to be elucidated.
METHODS: This study employed an integrated approach combining multi-omics bioinformatic mining with experimental validation. CCT5 expression patterns, genomic alterations, and their clinical relevance were evaluated using the TCGA, TIMER, and cBioPortal databases. The tumor immune microenvironment was characterized via the CIBERSORT algorithm. To validate these findings, immunohistochemistry (IHC) was performed on a clinical cohort of 107 COAD specimens. Functionally, shRNA-mediated stable knockdown was established in HCT116 and HT29 cell lines. The impact of CCT5 on malignant phenotypes was assessed through CCK-8, EdU, colony formation, and Transwell assays. Finally, the underlying molecular mechanisms were elucidated using Gene Set Variation Analysis (GSVA) and Western blotting to detect key components of the Wnt/β-catenin/Myc signaling axis.
RESULTS: CCT5 was significantly overexpressed in COAD at both the mRNA and protein levels, with high expression serving as an independent risk factor for poor overall survival and advanced clinicopathological stages (T, N, and AJCC stages). Exploratory genomic analysis indicated that CCT5 mutations were associated with poor prognosis. Immune profiling revealed a positive correlation between CCT5 levels and the infiltration of activated CD4 + memory T cells and M1 macrophages. In vitro assays demonstrated that CCT5 depletion markedly attenuated the proliferative, clonogenic, and metastatic potential of COAD cells. Mechanistically, our findings suggest that CCT5 may contribute to tumor progression by activating the Wnt/β-catenin/Myc cascade; its knockdown led to a significant downregulation of Wnt3a, nuclear β-catenin, c-Myc, and Cyclin D1.
CONCLUSIONS: Our findings identify CCT5 as a critical oncogenic driver in colon adenocarcinoma that facilitates tumor growth and metastasis by modulating the Wnt/β-catenin/Myc signaling pathway. These results highlight CCT5 may serve as a potential prognostic biomarker and a promising therapeutic target for precision oncology in COAD.
METHODS: This study employed an integrated approach combining multi-omics bioinformatic mining with experimental validation. CCT5 expression patterns, genomic alterations, and their clinical relevance were evaluated using the TCGA, TIMER, and cBioPortal databases. The tumor immune microenvironment was characterized via the CIBERSORT algorithm. To validate these findings, immunohistochemistry (IHC) was performed on a clinical cohort of 107 COAD specimens. Functionally, shRNA-mediated stable knockdown was established in HCT116 and HT29 cell lines. The impact of CCT5 on malignant phenotypes was assessed through CCK-8, EdU, colony formation, and Transwell assays. Finally, the underlying molecular mechanisms were elucidated using Gene Set Variation Analysis (GSVA) and Western blotting to detect key components of the Wnt/β-catenin/Myc signaling axis.
RESULTS: CCT5 was significantly overexpressed in COAD at both the mRNA and protein levels, with high expression serving as an independent risk factor for poor overall survival and advanced clinicopathological stages (T, N, and AJCC stages). Exploratory genomic analysis indicated that CCT5 mutations were associated with poor prognosis. Immune profiling revealed a positive correlation between CCT5 levels and the infiltration of activated CD4 + memory T cells and M1 macrophages. In vitro assays demonstrated that CCT5 depletion markedly attenuated the proliferative, clonogenic, and metastatic potential of COAD cells. Mechanistically, our findings suggest that CCT5 may contribute to tumor progression by activating the Wnt/β-catenin/Myc cascade; its knockdown led to a significant downregulation of Wnt3a, nuclear β-catenin, c-Myc, and Cyclin D1.
CONCLUSIONS: Our findings identify CCT5 as a critical oncogenic driver in colon adenocarcinoma that facilitates tumor growth and metastasis by modulating the Wnt/β-catenin/Myc signaling pathway. These results highlight CCT5 may serve as a potential prognostic biomarker and a promising therapeutic target for precision oncology in COAD.