Protein Expression Levels of the DCAF4-MEN1-hTERT Axis in Patients With Colon Adenocarcinoma and Their Relationship With Clinicopathological Characteristics and Prognosis

ZHU Shun, CHEN Siyuan, ZHENG Qin, LIU Hong

Abstract

Objective 

To explore the relationship between the expression levels of DNA damage binding protein 1 and cullin 4-related factor 4 (DCAF4) complex, which degrades the tumor suppressor menin 1 (MEN1)–human telomerase reverse transcriptase (hTERT) axis protein, and the clinicopathological characteristics and prognosis of patients with colon adenocarcinoma.

Methods 

Ninety-four patients with colon adenocarcinoma were included. The expression of DCAF4, MEN1, and hTERT in cancer tissues and adjacent tissues was detected by immunohistochemistry. The expression levels of DCAF4, MEN1, and hTERT in patients with different pathological grades and T stages were compared. Spearman rank correlation was used for correlation analysis, and survival analysis was conducted to investigate the impact of DCAF4, MEN1, and hTERT expression levels on the overall survival of patients with colon adenocarcinoma.

Results 

The expression levels of DCAF4 and MEN1 proteins in cancer tissues of colon adenocarcinoma patients (10.83 ± 2.89; 9.71 ± 3.57) were higher than those in adjacent tissues (2.39 ± 1.57; 4.92 ± 2.71, P < 0.001). The expression level of DCAF4 in patients with grade Ⅱ colon adenocarcinoma (14.16 ± 4.67) was lower than in patients with grade Ⅲ (20.79 ± 5.06, P < 0.01), while the expression of MEN1 (10.74 ± 3.06) was higher than in patients with grade Ⅲ (8.07 ± 2.88, P < 0.001), while there was no statistically significant difference in the protein expression scores of MEN1 and hTERT between the two groups. Compared with colon adenocarcinoma patients carrying the wild-type BRAF gene (5.47 ± 1.81), those with the mutant-type BRAF gene had a higher expression score of DCAF4 protein (9.30 ± 0.42, P < 0.001). The expression of MEN1 was correlated with the positive rate of PD1 (Spearman ρ = 0.219, P = 0.034). Compared with patients in stage T2 (3.93 ± 2.47), patients in stage T3 had a higher expression score of hTERT protein (6.25 ± 3.04, P < 0.05). Survival analysis showed that the expressions of MEN1, hTERT, and DCAF4 were not significantly associated with overall survival.

Conclusion 

High expression of DCAF4 and hTERT, as well as low expression of MEN1, is associated with unfavorable clinical and pathological features but has no significant relationship with prognosis.

 

Keywords: Colonic adenocarcinoma, DNA damage-binding protein 1 and cullin 4-associated factor 4 (DCAF4), Tumor suppressor menin 1 (MEN1), Human telomerase reverse transcriptase (hTERT), Clinicopathological characteristics, Overall survival

 

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