Biselli-Chicote Patrícia Matos, Biselli Joice Matos, Cunha Bianca R, Castro Rodrigo, Maniglia José Victor, Neto Dalísio de Santi, Tajara Eloiza Helena, Góis Filho José Franscisco de, Fukuyama Erica Erina, Pavarino Érika Cristina, Goloni-Bertollo Eny Maria
Genetics and Molecular Biology Research Unit, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil. Email:
Asian Pac J Cancer Prev. 2017 Aug 27;18(8):2171-2177. doi: 10.22034/APJCP.2017.18.8.2171.
Background: Overexpression of proangiogenic vascular endothelial growth factor A family VEGFAxxx is associated with tumor growth and metastasis. The role of the alternatively spliced antiangiogenic family VEGFAxxxb is poorly investigated in head and neck squamous cell carcinomas (HNSCCs). The antiangiogenic isoform binds to bevacizumab and its expression level could influence the treatment response and progression-free survival. In this study, the relative expression of VEGFAxxx and VEGFA165b isoforms and splicing regulatory factors genes was investigated in a series of HNSCCs. Methods: VEGFAxxx, VEGFA165b, SRSF6, SRSF5, SRSF1 and SRPK1 gene expression was quantified by quantitative real time PCR in 53 tissue samples obtained by surgery from HNSCC patients. Protein expression was evaluated by immunohistochemistry. Results: VEGFAxxx and VEGFA165b were overexpressed in HNSCCs. Elevated protein expression was also confirmed. However, VEGFA isoforms demonstrated differential expression according to anatomical sites. VEGFAxxx was overexpressed in pharyngeal tumors while the VEGFA165b isoform was up-regulated in oral tumors. The VEGFA165b isoform was also positively correlated with expression of the splicing regulatory genes SRSF1, SRSF6 and SRSF5. Conclusions: We concluded that VEGFAxxx and VEGFA165b isoforms are overexpressed in HNSCCs and the splicing regulatory factors SRSF1, SRSF6, SRSF5 and SRPK1 may contribute to alternative splicing of the VEGFA gene. The findings for the differential expression of the antiangiogenic isoform in HNSCCs could facilitate effective therapeutic strategies for the management of these tumors.
促血管生成的血管内皮生长因子A家族VEGFAxxx的过表达与肿瘤生长和转移相关。在头颈部鳞状细胞癌（HNSCC）中，可变剪接的抗血管生成家族VEGFAxxxb的作用研究较少。抗血管生成异构体与贝伐单抗结合，其表达水平可能影响治疗反应和无进展生存期。在本研究中，我们在一系列HNSCC中研究了VEGFAxxx和VEGFA165b异构体以及剪接调节因子基因的相对表达。方法：通过定量实时PCR对53例HNSCC患者手术获得的组织样本中的VEGFAxxx、VEGFA165b、SRSF6、SRSF5、SRSF1和SRPK1基因表达进行定量。通过免疫组织化学评估蛋白质表达。结果：VEGFAxxx和VEGFA165b在HNSCC中过表达。蛋白表达升高也得到证实。然而，VEGFA异构体根据解剖部位表现出差异表达。VEGFAxxx在咽部肿瘤中过表达，而VEGFA165b异构体在口腔肿瘤中上调。VEGFA165b异构体也与剪接调节基因SRSF1、SRSF6和SRSF5的表达呈正相关。结论：我们得出结论，VEGFAxxx和VEGFA165b异构体在HNSCC中过表达，剪接调节因子SRSF1、SRSF6、SRSF5和SRPK1可能有助于VEGFA基因的可变剪接。HNSCC中抗血管生成异构体差异表达的研究结果可能有助于制定有效的肿瘤治疗策略。
