Abstract
BackgroundChaperonin-containing TCP-1 (TRiC or CCT) was demonstrated to be involved in oncogenesis of cancers carcinogenesis and development of various malignancies. Increasing experimental evidence indicated that dysregulation of TRiC was implicated in the tumor progression of breast cancer (BCa). However, few definitive studies have addressed the diverse expression patterns and prognostic values of eight TRiC subunits. Thus, we aimed to investigate the clinical significance of TRiC subunit expression and prognostic values for their possible implications in diagnosis and treatment of BCa.MethodsBased on updated public resources and comprehensive bioinformatics analysis, we used some online databases (e.g., UALCAN, GEPIA, cBioPortal, TIMER, BC-GenExMiner, metascape, and GeneMANIA) to comprehensively explore the expression levels and the prognostic effects of eight TRiC subunits in patients with BCa.ResultsThe transcriptional levels of most subunits of the Chaperonin TRiC (CCT2, CCT3, CCT4, CCT5, CCT6A, and CCT7) were significantly elevated compared with normal breast tissues, whereas TCP1, CCT4, and CCT6B were lower in BCa tissues than in normal tissues. Besides, copy-number alterations (CNA) of eight TRiC subunits positively regulated their mRNA expressions. Furthermore, high mRNA expression of TCP1/CCT2/CCT4/CCT5/CCT6A/CCT7/CCT8 was significantly associated with poor overall survival (OS) in BCa patients. The eight subunits of the chaperonin TRiC was related to tumor purity and immune infiltration levels of BCa. Co-expression analysis showed CCT6B was negatively associated with other subunits of TRiC and other subunits of TRiC were positively correlated with each other. Additionally, TRiC and their interactive proteins were correlated with positive regulation of biological process, localization, and biological regulation.ConclusionThis study systematically illustrated the expression profiles and distinct prognostic values of chaperonin TRiC in BCa, providing insights for further investigation of subunits of the chaperonin TRiC as novel therapeutic targets and potential prognostic biomarkers in BCa.
Highlights
MATERIALS AND METHODSBreast cancer (BCa) ranks first in terms of morbidity and is the second leading cause of mortality among all female’s cancers globally, and 276,480 new cancer cases and 42,170 cancer deaths are expected in United States in 2020 according to the estimation by the American Cancer Society (Siegel et al, 2020)
The findings revealed that the expression of five genes was higher in breast cancer (BCa) samples than in normal control samples
When sorting the patients by subgroups, all subunits of the chaperonin TRiC were still significantly up-regulated in different molecular subtypes compared with paracancerous samples, except for CCT6B, which was down-regulated BCa patients (Figure 2G)
Summary
MATERIALS AND METHODSBreast cancer (BCa) ranks first in terms of morbidity and is the second leading cause of mortality among all female’s cancers globally, and 276,480 new cancer cases and 42,170 cancer deaths are expected in United States in 2020 according to the estimation by the American Cancer Society (Siegel et al, 2020). TRiC, known as CCT, is essential for cell viability and has been shown to assist the folding of cytoskeletal proteins (tubulins and actins) and other proteins related to carcinogenesis, such as p53, STAT3 (Signal transducer and activator of transcription 3) in an ATPdependent fashion (Amit et al, 2010; Trinidad et al, 2013; Kasembeli et al, 2014; Gestaut et al, 2019) Under such circumstances, elevated expression of TRiC subunits may lead to upregulation of these oncogenic proteins, concomitantly resulting in carcinogenesis.
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