EGFR突变型肺腺癌组织中VEGF-A蛋白的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2023.02.006

摘要/Abstract

摘要： 目的：探讨肺腺癌患者中血管内皮生长因子-A(VEGF-A)蛋白表达与表皮生长因子受体(EGFR)基因突变的关系，以及VEGF-A蛋白表达水平与患者临床病理指标及预后的关系。方法：收集经病理检查确诊为肺腺癌且经过EGFR基因检测并进行靶向治疗的患者72例，采用免疫组织化学法检测VEGF-A蛋白在EGFR突变型中晚期肺腺癌患者中的表达情况，采用门诊或者电话随访，统计患者无进展生存期。采用χ²检验、Kaplan-Meier生存分析、单因素、多因素Cox回归分析和评估VEGF-A蛋白表达与各病理指标间的关系，及与EGFR突变型肺腺癌患者预后的关系。结果：72例EGFR突变型肺腺癌组织中VEGF-A蛋白高表达率为70.83%(51/72)，主要位于肿瘤细胞的细胞质；VEGF-A蛋白高表达率在EGFR基因外显子19缺失和其他少见突变类型的肺腺癌患者间的差异无统计学意义(P>0.05)，而在不同临床分期及淋巴结转移情况患者间的差异具有统计学意义(P<0.05)；且与年龄、性别、吸烟史无明显相关(P>0.05)。Spearman秩相关分析显示，EGFR突变型肺腺癌患者的无进展生存期(PFS)与VEGF-A蛋白表达水平呈显著负相关(r=-0.513，P=0.009)。Kaplan-Meier生存分析结果显示VEGF-A高表达组患者的PFS明显小于VEGF-A低表达组；单因素分析结果显示淋巴结转移、临床分期及VEGF-A表达水平是影响患者预后的因素(HR分别为4.778、11.456、5.676)，多因素Cox回归分析结果显示临床分期、VEGF表达(HR分别为2.054、4.949)是影响患者生存预后的独立危险因素。结论：VEGF-A在EGFR突变的肺腺癌患者中高表达，与淋巴结转移和临床分期有关；VEGF-A表达与EGFR突变型肺腺癌患者PFS呈负相关，可能作为判断肺癌患者预后的指标。

关键词: 肺腺癌, 表皮生长因子受体, 血管内皮生长因子-A, 预后判断

Abstract: OBJECTIVE： To investigate relationships between vascular endothelial growth factor-A (VEGF-A) protein expression and epidermal growth factor receptor (EGFR) gene mutation in patients’ lung adenocarcinomas， as well as their implications as clinicopathological and prognosis indicators. METHODS： Lung adenocarcinoma tissues from 72 patients were evaluated for EGFR gene mutation VEGF-A protein in the middle-late EGFR mutation type (using immunohistochemical method). Patients were followed up to determine disease progression-free survival. The Chi-square test inspection，Kaplan-Meier survival analysis，single factor and multi-factors Cox regression analysis were used to evaluate the collected data. RESULTS：Among the 72 cases of type EGFR mutations，high expression of VEGF-A rate was 70.83% (51/72)，mainly in the cytoplasm of tumor cells. The difference in the high expression rate of VEGF-A protein expression was not statistically significant between patients with EGFR gene exon 19 deletion and other rare mutation types (P>0.05)， but statistically significant among patients with different clinical stages and lymph node metastasis status (P<0.05) There was no significant correlation with age，sex，and smoking history (P>0.05). Spearman rank correlation analysis showed that there was a significant negative correlation between progression-free survival (PFS) and VEGF-A protein expression in patients with EGFR-mutation (r=-0.513，P=0.009). The results of Kaplan-Meier survival analysis showed that the PFS of patients with high expression VEGF-A were significantly shorter than that of patients with low VEGF-A expression. The results of univariate analysis showed that lymph node metastasis， clinical stage and VEGF-A expression level were the factors affecting the prognosis of patients (HRs were 4.778，11.456，5.676，respectively). Multivariate COX regression analysis showed that clinical stage and VEGF expression (HRs were 2.054，4.949，respectively) were independent risk factors affecting survival and prognosis of patients. CONCLUSION： Relationships between VEGF-A in our patients with high expression of EGFR mutation and lymph node metastasis and clinical stages were statistically significant. VEGF-A expression and EGFR mutations and negative correlation PFS may be useful as an index of judging the prognosis of patients with lung cancer.

Key words: lung adenocarcinoma, epidermal growth factor receptor, vascular endothelial growth factor-A, prognosis judgment

中图分类号:

黄利丹, 吴月明, 王亚帝, 谭琦. EGFR突变型肺腺癌组织中VEGF-A蛋白的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(2): 116-120.

HUANG Lidan, WU Yueming, WANG Yadi, TAN Qi. Relationships between VEGF-A protein expression and EGFR mutation in patients with lung adenocarcinomas and its clinical significance[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 116-120.

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