The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Abstract

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

FOXP3‐regulated lncRNA NONHSAT136151 promotes colorectal cancer progression by disrupting QKI interaction with target mRNAs

“…Furthermore, we detected expression level of five key genes in DNA replication pathway in SW480 after silencing NONHSAT136151. Previous studies demonstrated the protumor function in CRC of the five genes, CDK2, 36 , 37 CHK2, 38 , 39 CDC6, 40 , 41 CHK1 42 and CDC25A. 43 In our study, all five genes expression was reduced to some extent and four genes (CDK2, CDC6, CHK1 and CDC25A) showed the significantly decreased expression (Figure 6I,J ), which can partly explain that decreased NONHSAT136151 expression leads to the inhibition of CRC progression.…”

CUL4A Ubiquitin Ligase Is an Independent Predictor of Overall Survival in Pancreatic Adenocarcinoma

“…In further agreement with overexpression of DNA replication-licensing factors in human PDAC, deregulation of replication licensing has been shown to cause replication stress, DNA damage and genomic instability, contributing to malignant transformation (41)(42)(43). In this context, we previously showed CDT1 to be overexpressed in colorectal cancer (21,44) and hepatocellular carcinoma (45), and several reports support the tumor-promoting roles of CDT1, CDC6 and MCM7 in other cancer types (45)(46)(47)(48)(49)(50). Interestingly, CDC6 disruption in pancreatic cancer cells leads to chromosomal instability and it is potentially linked to the KRAS signaling pathway (47,51,52).…”

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation

“…Furthermore, CHEK1 responds to DNA damage in CRC cells and TP53 status influences its function ( Gali-Muhtasib et al, 2008 ). CDC6 is overexpressed in CRC tissues and has been correlated with metastasis and prognosis ( Yang et al, 2022 ). Thus, CDC6 may serve as a valuable biomarker and a potential therapeutic target for CRC.…”