生长阻滞和DNA损伤诱导蛋白45A/G在前列腺癌组织中的表达及临床意义

    The Expression and Clinical Significance of Growth Arrest and DNA Damage Induced Protein 45A/G in Prostate Cancer Tissue

    • 摘要:
      目的 探讨生长阻滞和DNA损伤诱导蛋白45(growth arrest and DNA damage induced protein 45,Gadd45)A和Gadd45G在前列腺癌(prostate cancer,PCa)组织中的表达及其与临床病理特征和预后的关系。
      方法 选取2020年1月~2022年1月期间沧州市人民医院收治的80例PCa患者的癌组织作为PCa组,癌旁组织作为对照组,行前列腺根治术后随访3年,并根据术后复发情况将其分为复发组(n=31)和未复发组(n=49)。收集PCa患者临床病理特征资料;采用蛋白质免疫印迹法检测两组Gadd45A、Gadd45G表达情况,并分析其表达水平与患者临床病理特征的关系;绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估Gadd45A、Gadd45G对PCa患者术后复发预测价值;Cox回归分析影响PCa患者术后复发的风险因素。
      结果 PCa组Gadd45A和Gadd45G表达水平均明显低于对照组(0.79±0.16 vs. 1.00±0.26,0.60±0.14 vs. 0.98±0.23,P<0.05),且其低表达与PSA水平升高、TNM分期进展、淋巴结转移显著相关( \chi ^2 =10.570、9.642、9.657,P<0.05);复发PCa患者Gadd45A、Gadd45G表达水平明显低于未复发PCa患者(0.64±0.11 vs. 0.89±0.20,0.47±0.10 vs. 0.68±0.16,P<0.05),且Gadd45A、Gadd45G单独及联合预测PCa患者术后复发的曲线下面积(area under the curve,AUC)分别为0.824、0.813、0.922,联合优于单独预测(Z二者联合-Gadd45A=2.384、P=0.017,Z二者联合-Gadd45G=2.777,P=0.006);TNM分期风险比(hazard ratio,HR)=2.038,95%可信区间(confidence interval,CI) 1.161~3.577、淋巴结转移(HR=1.802,95%CI 1.093~2.970)、PSA水平(HR=1.736,95%CI 1.047~2.878)及Gadd45A(HR=0.925,95%CI 0.872~0.981)和Gadd45G(HR=0.766,95%CI 0.610~0.962)是PCa患者术后复发的影响因素(P<0.05)。
      结论 在PCa患者组织中,Gadd45A和Gadd45G表达水平降低,其表达水平与PSA水平、TNM分期、淋巴结转移有关,且二者对PCa患者术后复发的预测效能较高,具有一定的临床价值。

       

      Abstract:
      Objective To investigate the expression of growth arrest and DNA damage induced protein 45 (Gadd45) A and Gadd45G in prostate cancer (PCa) tissue and their relationship with clinical pathological features and prognosis.
      Methods The cancerous tissues of 80 patients with PCa admitted to our hospital between January 2020 and January 2022 were selected as the PCa group, and the paracancerous tissues were selected as the control group, which were followed up for 3 years after radical prostatectomy and divided into the recurrence group (n=31) and the non-recurrence group (n=49) according to the postoperative recurrence status. Clinical pathological characteristics data of PCa patients were collected. Western blotting was applied to detect the expression of Gadd45A and Gadd45G in two groups, and the relationship between their expression levels and the clinical pathological characteristics of patients was analyzed. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of Gadd45A and Gadd45G for postoperative recurrence in PCa patients. Cox regression was applied to analyze the risk factors affecting postoperative recurrence in PCa patients.
      Results Both Gadd45A and Gadd45G expression levels were significantly lower in the PCa group than in the control group (0.79±0.16 vs. 1.00±0.26, 0.60±0.14 vs. 0.98±0.23, P<0.05), and their low expression was associated with elevated PSA levels, increased TNM staging, and lymph node metastasis ( \chi ^2 =10.570, 9.642, 9.657, P<0.05). The expression levels of Gadd45A and Gadd45G in recurrent PCa patients were greatly lower than those in non-recurrent PCa patients (0.64±0.11 vs. 0.89±0.20, 0.47±0.10 vs. 0.68±0.16, P<0.05), and the area under the curve (AUC) of Gadd45A and Gadd45G alone and in combination in predicting postoperative recurrence in PCa patients was 0.824, 0.813, and 0.922, respectively, the combination was better than alone prediction (Z combination - Gadd45A=2.384, P=0.017, Z combination - Gadd45G=2.777, P=0.006). TNM staging (hazard ratio, HR)=2.038, 95% confidence interval (CI) 1.161~3.577, lymph node metastasis (HR=1.802, 95%CI 1.093~2.970), PSA levels (HR=1.736, 95%CI 1.047~2.878), and Gadd45A (HR=0.925, 95%CI 0.872~0.981) and Gadd45G (HR=0.766, 95%CI 0.610~0.962) were influencing factors for postoperative recurrence in PCa patients (P<0.05).
      Conclusion In the tissues of PCa patients, the expression levels of Gadd45A and Gadd45G are reduced, and their expression levels are related to PSA level, TNM staging, and lymph node metastasis. Moreover, both have high predictive efficacy for postoperative recurrence in PCa patients and have certain clinical value.

       

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