Yuan Xiao-Han, Yang Jie, Wang Xin-Yue, Zhang Xiao-Ling, Qin Ting-Ting, Li Kai
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Henan, Tianjin 300060, P.R. China.
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Henan, Tianjin 300060, P.R. China.
Oncol Lett. 2018 Aug;16(2):2105-2112. doi: 10.3892/ol.2018.8901. Epub 2018 Jun 5.
Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) are two of the most notable driver genes in lung cancer, whilst vascular endothelial growth factor (VEGF) signaling serves a critical function in tumor angiogenesis. However, few studies have focused on the potential connection between EGFR/KRAS mutational status, and VEGFA, VEGF receptor (VEGFR)1 and VEGFR2 expression in lung adenocarcinoma. EGFR (exon 19, 20 and 21) and KRAS (exon 2) mutations were detected using an amplification refractory mutation system technique, and the expression of VEGFA, VEGFR1 and VEGFR2 was analyzed using immunohistochemistry in 204 patients with lung adenocarcinoma. Associations between EGFR/KRAS mutational status and VEGFA, VEGFR1, and VEGFR2 expression was analyzed using Pearson χ tests. It was revealed that EGFR 21 exon (P=0.033) and EGFR 20 exon (P=0.002) mutated tumors exhibited a significantly higher level of expression of VEGFA. EGFR 21 exon mutant tumors additionally demonstrated a significantly higher level of co-expression of VEGFA and VEGFR1 (P<0.001). EGFR 19 exon mutation was significantly associated with low levels of VEGFR1 (P=0.008). KRAS mutation was significantly associated with a high level of co-expression of VEGFA, VEGFR1 and VEGFR2 (P=0.035), but no such association with the individual expression of VEGFA, VEGFR1 or VEGFR2 was identified. However, neither KRAS or EGFR mutations exhibited an association with the expression of VEGFR2. The present study may help in the treatment of various patients with KRAS or subtype of EGFR mutation with anti-angiogenesis therapy.
表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）是肺癌中两个最显著的驱动基因，而血管内皮生长因子（VEGF）信号传导在肿瘤血管生成中起关键作用。然而，很少有研究关注 EGFR/KRAS 突变状态与肺腺癌中血管内皮生长因子 A（VEGFA）、血管内皮生长因子受体（VEGFR）1 和 VEGFR2 表达之间的潜在联系。采用扩增阻滞突变系统技术检测 204 例肺腺癌患者的 EGFR（第 19、20 和 21 外显子）和 KRAS（第 2 外显子）突变，并采用免疫组织化学法分析 VEGFA、VEGFR1 和 VEGFR2 的表达。使用 Pearson χ检验分析 EGFR/KRAS 突变状态与 VEGFA、VEGFR1 和 VEGFR2 表达之间的关联。结果显示，EGFR 第 21 外显子（P = 0.033）和 EGFR 第 20 外显子（P = 0.002）突变的肿瘤 VEGFA 表达水平显著更高。EGFR 第 21 外显子突变的肿瘤还显示 VEGFA 和 VEGFR1 的共表达水平显著更高（P < 0.001）。EGFR 第 19 外显子突变与 VEGFR1 低水平显著相关（P = 0.008）。KRAS 突变与 VEGFA、VEGFR1 和 VEGFR2 的高共表达水平显著相关（P = 0.035），但未发现与 VEGFA、VEGFR1 或 VEGFR2 的单独表达有此类关联。然而，KRAS 或 EGFR 突变均与 VEGFR2 的表达无关联。本研究可能有助于采用抗血管生成疗法治疗各种 KRAS 或 EGFR 突变亚型的患者。
