English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Metastasis is a leading cause of death among cancer patients. In the tumor microenvironment, altered levels of extracellular matrix proteins, such as collagens, can facilitate the first steps of cancer cell metastasis, including invasion into surrounding tissue and intravasation into the blood stream. However, the degree of misexpression of collagen genes in tumors remains understudied, even though this knowledge could greatly facilitate the development of cancer treatment options aimed at preventing metastasis.    Methods  We systematically evaluate the expression of all 44 collagen genes in breast cancer and assess whether their misexpression provides clinical prognostic significance. We use immunohistochemistry on 150 ductal breast cancers and 361 cervical cancers and study DNA methylation in various epithelial cancers.    Results  In breast cancer, various tests show that  COL4A1  and  COL4A2  overexpression and  COL17A1  ( BP180 ,  BPAG2 ) underexpression provide independent prognostic strength (HR = 1.25, 95% CI = 1.17–1.34,  p  = 3.03 × 10 −10 ; HR = 1.18, 95% CI = 1.11–1.25,  p  = 8.11 × 10 −10 ; HR = 0.86, 95% CI = 0.81–0.92,  p  = 4.57 × 10 −6 ; respectively). Immunohistochemistry on ductal breast cancers confirmed that the  COL17A1  protein product, collagen XVII, is underexpressed. This strongly correlates with advanced stage, increased invasion, and postmenopausal status. In contrast, immunohistochemistry on cervical tumors showed that collagen XVII is overexpressed in cervical cancer and this is associated with increased local dissemination. Interestingly, consistent with the opposed direction of misexpression in these cancers, the  COL17A1  promoter is hypermethylated in breast cancer and hypomethylated in cervical cancer. We also find that the  COL17A1  promoter is hypomethylated in head and neck squamous cell carcinoma, lung squamous cell carcinoma, and lung adenocarcinoma, in all of which collagen XVII overexpression has previously been shown.    Conclusions  Paradoxically, collagen XVII is underexpressed in breast cancer and overexpressed in cervical and other epithelial cancers. However, the  COL17A1  promoter methylation status accurately predicts both the direction of misexpression and the increased invasive nature for five out of five epithelial cancers. This implies that aberrant epigenetic control is a key driver of  COL17A1  gene misexpression and tumor cell invasion. These findings have significant clinical implications, suggesting that the  COL17A1  promoter methylation status can be used to predict patient outcome. Moreover, epigenetic targeting of  COL17A1  could represent a novel strategy to prevent metastasis in patients.    Electronic supplementary material  The online version of this article (doi:10.1186/s13148-016-0290-6) contains supplementary material, which is available to authorized users.

In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion