FANCD2、PALB2表达水平与非小细胞肺癌临床特征及预后的关系

The relationship between the expressions of FANCD2 and PALB2 and the clinical manifestation and prognosis of patients with non-small cell lung cancer

摘要:

目的 探讨范科尼贫血D2蛋白（FANCD2）、乳腺癌易感基因2定位协作蛋白（PALB2）表达水平与非小细胞肺癌（NSCLC）临床特征及预后的关系。方法 选取2017年11月—2019年10月成都市第二人民医院收治的194例NSCLC患者作为研究对象。将手术过程中取得癌组织标本作为NSCLC组，将对应的癌旁组织标本作为癌旁组，每组194例。采用免疫组织化学法检测FANCD2、PALB2在NSCLC患者癌组织及癌旁组织中的表达情况；分析FANCD2、PALB2表达与NSCLC患者临床病理特征的关系；采用Kaplan-Meier法绘制生存曲线，采用Cox比例风险模型分析探讨NSCLC患者预后的影响因素。结果 NSCLC组FANCD2、PALB2阳性率高于癌旁组（P <0.05）。Spearman相关性分析显示，NSCLC患者癌组织中FANCD2蛋白与PALB2蛋白呈正相关（r_s =0.486，P <0.05）。不同年龄、性别、吸烟、组织学分型、肿瘤直径患者FANCD2、PALB2阳性率比较，差异均无统计学意义（P >0.05）。TNM分期为Ⅲ、Ⅳ期，低分化，有淋巴结转移患者高于TNM分期为I、Ⅱ期，中/高分化，无淋巴结转移患者（P <0.05）。多因素逐步Cox回归分析结果显示：TNM分期Ⅲ、Ⅳ期［H^R=4.125，（95% CI：2.187，10.035）］、低分化［H^R=3.146，（95% CI：3.115，9.264）］、淋巴结转移［H^R=4.124，（95% CI：3.005，13.145）］、FANCD2阳性［H^R=5.146，（95% CI：3.784，12.689）］、PALB2阳性［H^R=4.563，（95% CI：2.845，7.398）］是NSCLC患者复发的影响因素（P <0.05）。多因素逐步Cox回归分析结果显示，TNM分期Ⅲ/Ⅳ期［H^R=3.689，（95% CI：2.963，11.254）］、低分化［H^R=2.167，（95% CI：1.998，5.996）］、淋巴结转移［H^R=5.648，（95% CI：3.552，12.953）］、FANCD2阳性［H^R=3.886，（95% CI：2.958，12.775）］、PALB2阳性［H^R=4.633，（95% CI：1.968，11.547）］是NSCLC患者预后的影响因素（P <0.05）。FANCD2阳性患者与阴性患者生存率比较，差异有统计学意义（P <0.05）；PALB2阳性患者与阴性患者的生存率比较，差异有统计学意义（P <0.05）。结论 FANCD2、PALB2在NSCLC患者癌组织中呈高表达，与TNM分期、分化程度、淋巴结转移密切相关，可作为辅助评估患者预后和复发的潜在标志物。

Abstract:

Objective To explore the relationship between the expressions of Fanconi anemia D2 protein (FANCD2) and partner and localizer of BRCA2 (PALB2) and the clinical manifestations and prognosis of patients with non-small cell lung cancer (NSCLC).Methods A total of 194 patients with NSCLC admitted to our hospital from November 2017 to October 2019 were selected. The cancer tissue samples obtained during the surgery were included in the NSCLC group (n = 194), and the corresponding adjacent tissue samples were included in the adjacent group (n = 194). Immunohistochemistry was used to detect the expressions of FANCD2 and PALB2 in NSCLC tissues and adjacent tissues. The relationship between the expressions of FANCD2 and PALB2 and the clinicopathological characteristics of NSCLC patients was analyzed. Kaplan-Meier method was applied to plot survival curves, and the Cox proportional hazard model was used to analyze the factors affecting the prognosis of patients with NSCLC.Results The positive rates of FANCD2 and PALB2 in the NSCLC group were higher than those in the adjacent group (P < 0.05). Spearman correlation analysis revealed that the expression of FANCD2 was positively correlated with that of PALB2 in cancer tissues of NSCLC patients (r_s = 0.486, P < 0.05). There was no significant difference in the positive rates of FANCD2 and PALB2 among patients with different age, gender, smoking behavior, histological type of the tumor, and tumor diameter (P < 0.05). The positive rates of FANCD2 and PALB2 in patients with TNM stage III and IV tumors, poorly-differentiated tumors, and lymph node metastasis were higher than those in patients with TNM stage I and II tumors, moderately- and well-differentiated tumors, and no lymph node metastasis (P < 0.05). The multivariable Cox regression analysis exhibited that TNM stage III/IV tumors [H^R = 4.125, (95% CI: 2.187, 10.035) ], poorly-differentiated tumors [H^R = 3.146, (95% CI: 3.115, 9.264) ], lymph node metastasis [H^R = 4.124, 95% CI: 3.005, 13.145) ], FANCD2 positivity [H^R = 5.146, (95% CI: 3.784, 12.689) ], and PALB2 positivity [H^R = 4.563, (95% CI:2.845, 7.398) ] were factors affecting the recurrence in NSCLC patients (P < 0.05), and that TNM stage III/IV tumors [H^R = 3.689, (95% CI: 2.963, 11.254) ], poorly-differentiated tumors [H^R = 2.167, (95% CI: 1.998, 5.996) ], lymph node metastasis [H^R = 5.648, (95% CI: 3.552, 12.953) ], FANCD2 positivity [H^R = 3.886, (95% CI: 2.958, 12.775)], and PALB2 positivity [H^R = 4.633, (95% CI: 1.968, 11.547) ] were factors affecting the prognosis of NSCLC patients (P < 0.05). The survival rates of FANCD2-positive patients were significantly different from those of FANCD2-negative patients (P < 0.05), and the survival rates of PALB2-positive patients were also significantly different from those of PALB2-negative patients (P < 0.05).Conclusions FANCD2 and PALB2 are highly expressed in cancer tissues of NSCLC patients and closely related to TNM stage, tumor differentiation and lymph node metastasis, and can be established as potential biomarkers for evaluating the recurrence and prognosis in NSCLC patients.