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. 2022 Jun 6;11(11):1852.
doi: 10.3390/cells11111852.

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Lui Ng  1 , Hung-Sing Li  1 , Abraham Tak-Ka Man  1 , Ariel Ka-Man Chow  1 , Dominic Chi-Chung Foo  1 , Oswens Siu-Hung Lo  1 , Roberta Wen-Chi Pang  1 , Wai-Lun Law  1
Affiliations

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Lui Ng et al. Cells. .

Abstract

Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients.

Methods: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR. CBX8 protein level in CRC and NAT specimens from 66 patients was determined by immunohistochemistry. CBX8 gene and protein levels were correlated with the patients' clinicopathological parameters and circulatory immune cell profiles. The association between CBX8 and pluripotency-associated genes was analyzed using the TCGA database.

Results: NAT CBX8 gene level positively correlated with TNM stage, tumor invasion, lymph node metastasis and distant metastasis, indicating its association with tumor progression and metastasis. There was no correlation between NAT CBX8 protein level and clinicopathological parameters. Moreover, a high level of CBX8 gene and protein in NAT both correlated with poor DFS and OS. There was an inverse correlation between CBX8 gene level and post-operative platelet counts and platelet to lymphocyte level, suggesting its association with systematic inflammation. Finally, TCGA analysis showed that CBX8 level was correlated with a couple of pluripotency-associated genes, supporting its association with cancer stemness.

Conclusions: High NAT CBX8 is a poor prognostic factor for tumor progression and survival in CRC patients.

Keywords: CBX8; colorectal cancer; normal tissue adjacent to the tumor (NAT); prognostic biomarker.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical significance of CBX8 expression in CRC patients. (A) The CBX8 gene was significantly overexpressed in CRC when compared to paired NAT tissue (n = 95). (B) The CBX8 protein level was significantly higher in CRC when compared to paired NAT tissue (n = 66). (C) Representative IHC stainings of CBX8 in patient #490 showed higher CBX8 level in CRC compared to paired NAT (Magnification: 40×). (D) A significant correlation was observed between CBX8 gene and protein levels within the NAT tissue (n = 66).
Figure 2
Figure 2
Correlation between CBX8 level and survival of CRC patients. (A,B) CRC patients with high NAT CBX8 gene levels, compared to those with low NAT CBX8 levels, have a significantly poorer (A) disease-free survival and (B) overall survival. (C,D) CRC patients with high NAT CBX8 protein levels, compared to those with low NAT CBX8 levels, have a significantly poorer (C) disease-free survival and (D) overall survival. (E,F) CRC patients with high CRC CBX8 protein levels, compared to those with low CRC CBX8 levels, have a significantly poorer (E) disease-free survival and (F) overall survival.
Figure 3
Figure 3
Correlation between NAT or CRC CBX8 gene expression and blood immune cell profiles in CRC patients. (A,B) NAT CBX8 level was inversely correlated with level of (A) platelets (PLT) and (B) platelet to lymphocyte ratio (PLR) in post-operative blood of CRC patients. (C) NAT CBX8 level showed a positive trend with level of post-operative CEA. (D) Tumor CBX8 level was positively correlated with post-operative LMR level. (E,F) Tumor CBX8 level was inversely and positively correlated with dymamic changes (post-operative minus pre-operative) in (E) LMR level and (F) eosinophil level, respectively.
Figure 4
Figure 4
Correlation between NAT or CRC CBX8 protein level and blood immune cell profiles in CRC patients. (A) The CRC CBX8 level was inversely correlated with dyanmic changes (post-operative minus pre-operative) in eosinophil level. (B,C) CBX8 protein levels in (B) NAT and (C) CRC were positively correlated with post-operative CEA level. (D,E) CBX8 protein levels in (D) NAT and (E) CRC were positively correlated with dynamic changes (post-operative minus pre-operative) in CEA level.
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