Stefansson Ingunn M, Raeder Maria, Wik Elisabeth, Mannelqvist Monica, Kusonmano Kanthida, Knutsvik Gøril, Haldorsen Ingfrid, Trovik Jone, Øyan Anne M, Kalland Karl-H, Staff Anne Cathrine, Salvesen Helga B, Akslen Lars A
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Oncotarget. 2015 Apr 30;6(12):10634-45. doi: 10.18632/oncotarget.3521.
Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel proliferation is associated with gene expression profiles or copy number alterations in endometrial cancer.
A prospective series of endometrial carcinomas was studied for angiogenesis markers, gene expression profiles, and gene copy number data. For validation, an independent series of endometrial carcinomas as well as an external cohort of endometrial cancer patients were examined by gene expression microarrays.
Increased microvessel proliferation (MVP) was associated with aggressive tumor features and reduced survival, and a 32-gene expression signature was found to separate tumors with high versus low MVP. An increased 32-gene signature score was confirmed to associate with high-grade tumor features and reduced survival by independent cohorts. Copy number studies revealed that amplification of the 6p21 region was significantly associated with MVP, a high 32-gene score, as well as reduced survival.
Increased MVP was significantly associated with aggressive endometrial cancer and reduced survival. Integrated analyses demonstrated significant associations between increased vascular proliferation, amplification of the 6p21 region, VEGF-A mRNA expression, and the 32-gene angiogenesis signature. Our findings indicate amplification of 6p21 as a possible driver of tumor vascular proliferation in endometrial cancer.
血管生成是癌症的一个标志。本研究的目的是探讨微血管增殖是否与子宫内膜癌的基因表达谱或拷贝数改变相关。
对一系列前瞻性子宫内膜癌病例进行血管生成标志物、基因表达谱和基因拷贝数数据研究。为进行验证，通过基因表达微阵列对另一独立系列的子宫内膜癌病例以及一组子宫内膜癌患者外部队列进行检测。
微血管增殖增加（MVP）与侵袭性肿瘤特征及生存率降低相关，并且发现一个32基因表达特征可区分高MVP与低MVP的肿瘤。独立队列证实，32基因特征评分增加与高级别肿瘤特征及生存率降低相关。拷贝数研究显示，6p21区域的扩增与MVP、高32基因评分以及生存率降低显著相关。
MVP增加与侵袭性子宫内膜癌及生存率降低显著相关。综合分析表明，血管增殖增加、6p21区域扩增、VEGF-A mRNA表达以及32基因血管生成特征之间存在显著关联。我们的研究结果表明，6p21扩增可能是子宫内膜癌肿瘤血管增殖的驱动因素。
