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Archive > Volume 31 Issue 9 > 2024,31(9):895-906. DOI:10.3872/j.issn.1007-385X.2024.09.008 Prev Next
Clinical Research
Expression of CCT subunits in thyroid cancer and their impacts on clinical prognosis，tumor microenvironment and chemotherapy drug sensitivity of patients
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Abstract:
Objective: To investigate the expression of eight subunits of chaperonin containing t-complex 1 (CCT) in thyroid cancer (TC) tissues and their correlation with TC staging, patient prognosis, immune cell infiltration, immune checkpoint expression, and chemotherapy drug sensitivity. Methods: Data from The Cancer Genome Atlas (TCGA) database were used to analyze the expression of each CCT subunit in TC tissues and para-cancerous tissues as well as their relationship with the prognosis of TC patients. The biological function of each CCT subunit was analyzed by the Gene Set Enrichment Analysis (GSEA). Data from the TCGA and TIMER2.0 databases were used to analyze the correlations between the expression of each CCT subunit and the tumor microenvironment, infiltration of immune cells, chemotherapeutic drug sensitivity, and immune checkpoint expression. Results: Database analysis showed high mRNA expression of CCT3, CCT7, and CCT8 and low mRNA expression of CCT1, CCT2, CCT5, and CCT6B in TC tissues (P < 0.01 or P < 0.001). CCT3, CCT6B, and CCT8 mRNA expression were correlated with T staging (P < 0.05 or P < 0.01); CCT6B mRNA expression was associated with lymph node metastasis (P < 0.01); CCT5 mRNA expression was associated with distant metastasis (P < 0.05); and CCT6B may serve as an independent prognostic biomarker for overall survival (OS) in TC patients. CCT subunit expression was primarily enriched in signaling pathways such as graft rejection, complement, and interferongamma.Low expression groups of CCT subunits demonstrated significantly higher TC stromal score, immune infiltration score and composite score than the high expression groups (P < 0.05 or P < 0.01 or P < 0.001), displaying a negative correlation between the expression of each CCT subunit and TC stromal, immune infiltration and composite scores (all P < 0.01). The mRNA expression of each CCT subunit was positively correlated with CD8+ T cell and macrophage infiltration (all P < 0.05), the mRNA expression of most CCT subunits (except CCT6B and CCT7) was positively correlated with neutrophil infiltration (P < 0.05 or P < 0.01 or P < 0.001), whereas the mRNA expression of CCT3, 4, 7, and 8 was negatively correlated with CD4+ T-cell infiltration (all P < 0.05). Compared to the low-expression group, patients with high mRNA expression of most CCT subunit had significantly higher IC50 for chemotherapeutic agents such as sorafenib, levatinib, darafenib, trametinib, vandetanib, and cabozantinib (all P < 0.05 or P < 0.01 or P < 0.001). CCT subunit expression in TC tissues was significantly correlated with the expression of PD-1, PD-L1, PD-L2, CTLA4, CD80, and CD86 (P < 0.05 or P < 0.01 or P < 0.001). Conclusion: CCT complexes may promote TC development by affecting the tumor microenvironment thus impacting patient prognosis, potentially serving as a target for the diagnosis and immunotherapy of refractory TC.
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