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Increased angiogenesis is associated with a 32-gene expression signature and 6p21 amplification in aggressive endometrial cancer.

Stefansson IM, Raeder M, Wik E, Mannelqvist M, Kusonmano K, Knutsvik G, Haldorsen I, Trovik J, Øyan AM, Kalland KH, Staff AC, Salvesen HB, Akslen LA - Oncotarget (2015)

Bottom Line: Angiogenesis is a hallmark of cancer.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Correlations betweenA: the 32-gene signature score and a VEGF-signature [25]; B: the 32-gene signature score and VEGF mRNA expression; C: Correlation between microvessel proliferation (MVP) and VEGF mRNA expression. The Spearman rank correlation test was used for bivariate correlations.
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Figure 2: Correlations betweenA: the 32-gene signature score and a VEGF-signature [25]; B: the 32-gene signature score and VEGF mRNA expression; C: Correlation between microvessel proliferation (MVP) and VEGF mRNA expression. The Spearman rank correlation test was used for bivariate correlations.

Mentions: We next examined the correlation between our 32-gene score and 6 different gene signatures previously reported to reflect angiogenesis and outcome in a range of cancers: a VEGF signature [25], a vascular invasion signature [26], a wound response signature [27], a hypoxia gene signature [28], a TGFβ gene-response signature of human epithelial cells [29] and a BMI-1 driven stemness related gene signature [30]. All signatures tended to or were significantly correlated to the present 32-gene vascular proliferation signature, as shown in Supplementary Table 2. Figure 2 illustrates this significant correlation between the VEGF-A signature and our 32-gene score (Spearman's rho correlation 0.44; P<0.001), as well as the correlation between VEGF-A mRNA and microvessel proliferation in our series (Figure 2A-C).


Increased angiogenesis is associated with a 32-gene expression signature and 6p21 amplification in aggressive endometrial cancer.

Stefansson IM, Raeder M, Wik E, Mannelqvist M, Kusonmano K, Knutsvik G, Haldorsen I, Trovik J, Øyan AM, Kalland KH, Staff AC, Salvesen HB, Akslen LA - Oncotarget (2015)

Correlations betweenA: the 32-gene signature score and a VEGF-signature [25]; B: the 32-gene signature score and VEGF mRNA expression; C: Correlation between microvessel proliferation (MVP) and VEGF mRNA expression. The Spearman rank correlation test was used for bivariate correlations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496381&req=5

Figure 2: Correlations betweenA: the 32-gene signature score and a VEGF-signature [25]; B: the 32-gene signature score and VEGF mRNA expression; C: Correlation between microvessel proliferation (MVP) and VEGF mRNA expression. The Spearman rank correlation test was used for bivariate correlations.
Mentions: We next examined the correlation between our 32-gene score and 6 different gene signatures previously reported to reflect angiogenesis and outcome in a range of cancers: a VEGF signature [25], a vascular invasion signature [26], a wound response signature [27], a hypoxia gene signature [28], a TGFβ gene-response signature of human epithelial cells [29] and a BMI-1 driven stemness related gene signature [30]. All signatures tended to or were significantly correlated to the present 32-gene vascular proliferation signature, as shown in Supplementary Table 2. Figure 2 illustrates this significant correlation between the VEGF-A signature and our 32-gene score (Spearman's rho correlation 0.44; P<0.001), as well as the correlation between VEGF-A mRNA and microvessel proliferation in our series (Figure 2A-C).

Bottom Line: Angiogenesis is a hallmark of cancer.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus