FGFR1 is associated with c-MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti-angiogenic therapy
FGFR1 is associated with c-MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti-angiogenic therapy
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DOI：
10.1111/his.14076
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发表时间：
2020-04-28
期刊：
影响因子：
6.4
通讯作者：
Go, Heounjeong
中科院分区：
文献类型：
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作者：
Park, Jee Young;Kim, Pil-Jong;Go, Heounjeong
目的探讨FGFR1和c-myc在肾透明细胞癌中的表达及其与血管生成的关系。方法采用免疫组织化学和荧光原位杂交技术，对91例接受血管内皮生长因子受体酪氨酸激酶抑制剂(VEGFR-TKIs)治疗的转移性肾细胞癌患者进行免疫组织化学和荧光原位杂交。分析肿瘤基因组图谱(TCGA)中血管生成分子FGFR1和c-MYC的表达及肿瘤血管密度(TVD)、肿瘤血管密度(TVD)和mRNA表达。29.1%的肿瘤表达FGFR1，74.4%的肿瘤表达pFGFR1，30.8%的肿瘤表达c-myc。FGFR1(高)是影响总生存率(HR=1.871，P=0.032)和无进展生存率(HR=1.976，P=0.016)的独立预后因素。FGFR1HIGH与VEGFR-TKI反应性显著相关(P=0.011)。FGFR1HIGH/c-MYChigh与血管生成前标志物呈正相关(P=0.018)和HIF-1α(P<；0.0001)。FGFR1(高)/c-MYChigh肿瘤显示出更高的TVD值以及更高的VEGFR2和PDGFFR-β表达(P<；0.0001)。结论FGFR1和c-MYC可能参与肿瘤血管生成，FGFR1可能是转移性肾细胞癌的治疗靶点。
Aims This study aimed to investigate the clinicopathological significance of FGFR1 and c-MYC expression, particularly in relation to angiogenesis in clear cell renal cell carcinoma (CCRCC).Methods and results Immunohistochemistry and fluorescence in-situ hybridisation were conducted with tissue microarrays from 91 metastatic CCRCC patients who received VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs). The expression of angiogenic molecules, FGFR1 and c-MYC, and tumoral vascular density (TVD) and mRNA expression and TVD of 533 CCRCCs in The Cancer Genome Atlas (TCGA) were analysed. FGFR1, pFGFR1 and c-MYC expression was observed in 29.1, 74.4 and 30.8% of tumours, respectively. FGFR1(high) was an independent worse prognostic factor for overall (HR = 1.871, P = 0.032) and progression-free (HR = 1.976, P = 0.016) survival. FGFR1(high) was significantly related to VEGFR-TKI responsiveness (P = 0.011). The presence of FGFR1(high)/c-MYChigh showed a positive correlation with proangiogenic markers, including VEGF (P = 0.018) and HIF-1 alpha (P < 0.0001). FGFR1(high)/c-MYChigh tumours showed higher TVDs together with higher VEGFR2 and PDGFR-beta expression (both P < 0.0001). FGFR1 and c-MYC expression was also positively correlated with the expression of hypoxia-related and proangiogenic-related genes in the TCGA data.Conclusions FGFR1 and c-MYC may be involved in tumour angiogenesis and FGFR1 may represent a promising therapeutic target in metastatic CCRCC.