Molecular and clinical characterization of CCT2 expression at transcriptional level via 2994 samples of breast cancer

Liu, Qiang; Qi, Yu; Wang, Xiangyu; Kong, Xiangyi; Fang, Yi; Wang, Jing

doi:10.21203/rs.3.rs-44221/v1

Cited by 2 publications

(1 citation statement)

References 34 publications

(40 reference statements)

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“…[4,8,9]. Data from our lab and others revealed that the CCT2 subunit, or CCTβ, is linked to cancer progression and increased stage/aggressiveness of breast, lung, prostate, hepatocellular, gallbladder, and colonic cancer [10][11][12][13][14][15][16][17][18]. Additionally, we found that the level of CCT2 was independent of hormone receptor status in breast cancer [12], suggesting that CCT2 expression could be upstream of tumor lineage-defining markers.…”

Section: Introductionsupporting

confidence: 55%

Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood

et al. 2022

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Herein we report the use of Chaperonin-Containing TCP-1 (CCT or TRiC) as a marker to detect circulating tumor cells (CTCs) that are shed from tumors during oncogenesis. Most detection methods used in liquid biopsy approaches for enumeration of CTCs from blood, employ epithelial markers like cytokeratin (CK). However, such markers provide little information on the potential of these shed tumor cells, which are normally short-lived, to seed metastatic sites. To identify a marker that could go beyond enumeration and provide actionable data on CTCs, we evaluated CCT. CCT is a protein-folding complex composed of eight subunits. Previously, we found that expression of the second subunit (CCT2 or CCTβ) inversely correlated with cancer patient survival and was essential for tumorigenesis in mice, driving tumor-promoting processes like proliferation and anchorage-independent growth. In this study, we examined CCT2 expression in cancer compared to normal tissues and found statistically significant increases in tumors. Because not all blood samples from cancer patients contain detectable CTCs, we used the approach of spiking a known number of cancer cells into blood from healthy donors to test a liquid biopsy approach using CCT2 to distinguish rare cancer cells from the large number of non-cancer cells in blood. Using a clinically validated method for capturing CTCs, we evaluated detection of intracellular CCT2 staining for visualization of breast cancer and small cell lung (SCLC) cancer cells. We demonstrated that CCT2 staining could be incorporated into a CTC capture and staining protocol, providing biologically relevant information to improve detection of cancer cells shed in blood. These results were confirmed with a pilot study of blood from SCLC patients. Our studies demonstrate that detection of CCT2 could identify rare cancer cells in blood and has application in liquid biopsy approaches to enhance the use of minimally invasive methods for cancer diagnosis.

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Section: Introductionsupporting

confidence: 55%

Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood

et al. 2022

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Molecular and Clinical Characterization of CCT2 Expression and Prognosis via Large-Scale Transcriptome Profile of Breast Cancer

Liu

Kong

et al. 2021

Front. Oncol.

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Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

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Molecular and clinical characterization of CCT2 expression at transcriptional level via 2994 samples of breast cancer

Cited by 2 publications

References 34 publications

Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood

Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood

Molecular and Clinical Characterization of CCT2 Expression and Prognosis via Large-Scale Transcriptome Profile of Breast Cancer

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