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结肠腺癌患者DCAF4-MEN1-hTERT轴的蛋白表达水平与其临床病理特征及预后的关系

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

    摘要
  • 摘要:
    目的 探究结肠腺癌患者DNA损伤结合蛋白1和cullin 4相关因子4（DCAF4）-复合物通过降解肿瘤抑制因子menin 1（MEN1）-人端粒酶逆转录酶 （hTERT）轴蛋白表达水平与临床病理特征及预后的关系。
    方法 纳入结肠腺癌患者94例，采用免疫组化检测患者癌组织及癌旁组织样本中DCAF4、MEN1及hTERT的表达情况。比较结肠腺癌患者不同病理分级及不同T分期之间DCAF4、MEN1及hTERT蛋白表达水平，用Spearman秩相关进行相关性检验，再对DCAF4、MEN1及hTERT表达水平与结肠腺癌患者总生存期的影响进行生存分析。
    结果 结肠腺癌患者癌组织中DCAF4、MEN1蛋白表达水平（10.83±2.89；9.71±3.57）高于癌旁组织（2.39±1.57；4.92±2.71，P<0.001）。同时，Ⅱ级结肠腺癌患者DCAF4表达水平（14.16±4.67）低于Ⅲ级患者（20.79±5.06，P<0.01），MEN1表达（10.74±3.06）高于Ⅲ级患者（8.07±2.88，P<0.001）。与携带野生型BRAF基因结肠腺癌患者（5.47±1.81）相比，携带突变型BRAF基因患者DCAF4蛋白表达评分更高（9.30±0.42，P<0.001），而两者的MEN1和hTERT蛋白表达评分差异无统计学意义。MEN1表达与PD1阳性率相关（Spearman ρ= 0.219，P=0.034）。与T2期患者（3.93±2.47）相比，T3期患者hTERT蛋白表达评分更高（6.25±3.04，P<0.05）。生存分析显示MEN1、hTERT、DCAF4表达与患者总生存无显著关联。
    结论 高表达DCAF4、hTERT，低表达MEN1与不良临床病理特征有关，但与预后关系不显著。

     

    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.

     

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