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. 2023 Apr 15:2023:9057735.
doi: 10.1155/2023/9057735. eCollection 2023.

Dickkopf 4 Alone and in Combination with Leucyl-tRNA Synthetase as a Good Prognostic Biomarker for Human Colorectal Cancer

Su-Jeong Park  1   2   3 , Jun Gi Cho  1   2   3 , Sang-Heum Han  1   2   3 , Yu-Mi Kim  4 , Min-Gyoung Pak  5 , Mee-Sook Roh  5 , Joo-In Park  1   2   3
Affiliations

Dickkopf 4 Alone and in Combination with Leucyl-tRNA Synthetase as a Good Prognostic Biomarker for Human Colorectal Cancer

Su-Jeong Park et al. Biomed Res Int. .

Abstract

The prognosis of patients with colorectal cancer (CRC) is affected by invasion and metastasis. Leucyl-tRNA synthetase (LARS) was shown to be related to the growth and migration of lung cancer cells. Dickkopf 4 (DKK4) is known as a Wnt/β-catenin pathway inhibitor, and its upregulation was reported in several cancers. However, the clinical significance of LARS and DKK4 in human CRC has not been clearly defined. We investigated the expression of LARS and DKK4 by immunohistochemical staining in tissue microarrays from 642 primary CRC patients and analyzed the relationship between their expression and the clinicopathological characteristics of CRC patients. LARS and DKK4 expressions were not related to gender, age at surgery, histologic grade, size, tumor location, tumor invasion, or metastasis, but LARS expression was significantly correlated with TNM stage, N stage, and lymph node metastasis. DKK4 expression was inversely related to the TNM stage and N stage. Survival analysis demonstrated that the OS and DFS in the LARS high expression group were not different compared to the LARS low expression group. OS and DFS in the DKK4 high expression group were significantly higher than in the DKK4 low expression group. In addition, OS and DFS in the group with the combination of the LARS high/DKK4 low expression were significantly lower than in the LARS high/DKK4 high expression group. The low expression of DKK4 alone can be used as a predictor of relapse in CRC patients. In addition, DKK4 low expression in the case of LARS high expression can be used as a poor prognostic factor in CRC patients. Thus, our findings suggest that DKK4 alone or in combination with LARS at diagnosis may be a useful prognostic factor for CRC.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Representative illustrations of immunohistochemical staining for LARS and DKK4 in CRC tissue. (a) Upper: LARS high expression in colorectal cancer tissue. Lower: LARS low expression in colorectal cancer tissue. (b) Upper: DKK4 high expression in colorectal cancer tissue. Lower: DKK4 low expression in colorectal cancer tissue. Magnification 200x for all panels.
Figure 2
Figure 2
The Kaplan-Meier survival curves in 642 patients with CRC according to the expression levels of LARS and DKK4 and the combination of LARS and DKK4 expression levels. (a) The Kaplan-Meier survival curves for OS in CRC patients. The patients were dichotomized according to LARS expression. (b) The Kaplan-Meier survival curves for DFS in CRC patients. The patients were dichotomized according to LARS expression. (c) The Kaplan-Meier survival curves for OS in CRC patients. The patients were dichotomized according to DKK4 expression. (d) The Kaplan-Meier survival curves for DFS in CRC patients. Patients dichotomized according to DKK4 expression. (e) The Kaplan-Meier survival curves for OS in 642 CRC patients according to the combination of LARS and DKK4 expression levels. (f) The Kaplan-Meier survival curves for DFS in 642 CRC patients according to the combination of LARS and DKK4 expression levels. OS: overall survival; DFS: disease-free survival.
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