Molecular profiling of cervical cancer progression

Abstract

Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up-and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-b) were upregulated at least two-fold. Some of these genes (AKT and MMP3) are key regulators of epithelial -mesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer.

SIX1 Promotes Tumor Lymphangiogenesis by Coordinating TGFβ Signals That Increase Expression of VEGF-C

“…Moreover, higher VEGF-C expression in cervical cancer is associated with higher densities of peritumoral lymphatic vessels, increased lymphatic invasion, and increased lymph node metastasis (28). Higher TGFb1 expression is also associated with lymph node metastasis and poor prognosis of cervical cancer (29,30). On the basis of these premises, in this study, we investigated whether SIX1 and TGFb were responsible for modulating VEGF-C expression and lymphangiogenesis in cervical cancer.…”

A TaqMan Low-Density Array to Predict Outcome in Advanced Hodgkin's Lymphoma Using Paraffin-Embedded Samples

“…Hundreds of reactions can be done simultaneously, enabling large numbers of cases to be rapidly assessed. These technologies would be especially useful for identifying gene signatures of prognostic significance (42) and have already been shown to be useful in other tumor types (43). Thus, we have built a novel TLDA assay that includes genes known to be involved in Hodgkin's lymphoma pathogenesis and that could be related to treatment response.…”

Deregulated Expression of Superoxide Dismutase-2 Correlates with Different Stages of Cervical Neoplasia

“…Thus, most of the current efforts in this field have been dedicated to the investigation of genes that are differentially expressed in cervical cancer when compared to their normal tissue counterparts. However, robust findings have shown that no more than a subset of these genes is associated with cancer progression and metastatic phenotype [10]. Using microarray approach we have compared the global transcription profile of normal and HPV-immortalized keratinocytes, upon TNFα treatment.…”