Endometrial Cancer Analysis Finds Proteins Linked to Tumor Progression

At this year’s Immunology meeting in Washington, DC, we presented results from a new study of metastatic progression in endometrial cancer. Scientists Jean-Noel Billaud, PhD, Stuart Tugendreich, PhD, and Debra Toburen used Biomedical Genomics Workbench and Ingenuity Pathway Analysis (IPA) to reanalyze previously published data, finding new elements that may be associated with cancer progression.

 

 

The poster reporting this project is “Identification of potential immune targets in controlling Endometrioid Endometrial Carcinoma metastatic progression.” Endometrioid endometrial carcinoma (EEC) is the most common subtype of endometrial adenocarcinoma, which affects hundreds of thousands of women globally. According to the National Cancer Institute, more than 60,000 women in the U.S. will be diagnosed with endometrial cancer this year. EEC is estrogen-dependent, with risk factors including menopause, obesity, and diabetes, among others.

Through this project, our scientists aimed to learn more about how tumors evolve in patients with EEC, which typically presents as a low-grade tumor confined to the uterus (known as stage 1) but in as many as 20% of cases has already metastasized. Late-stage diagnosis has devastating implications: women with localized cancer have a stunning five-year survival rate of 95%, while women whose cancer has metastasized have just a 16% survival rate after five years.

The team used a publicly available data set of RNA sequencing data generated from tissues collected during surgery from three women, all with stage 1 EEC. The idea was simple: could different analysis tools glean new information from the previously collected data? “We hoped to add some different parameters and contribute to this important subject,” Billaud says, noting that all results in the poster will require further validation.

The raw data was run through Biomedical Genomics Workbench for mapping, quantification, and differential expression analysis with no bioinformatics expertise required. Results were then sent directly to IPA for interpretation. This approach led to the identification of three proteins related to immune function that appear to be involved in cell invasion, metastasis, and epithelial-to-mesenchymal transition — all important elements of tumor progression. The focus on this class of proteins was intentional, Billaud says, because they are likely to be targetable with therapies and could have the most immediate benefit for cancer patients.

 

Learn more about Biomedical Genomics Workbench or IPA.

 

Meet us in D.C. at Immunology 2017 on May 12–16!

Drop by and meet our scientists at QIAGEN booth #132 to get insights into advanced bioinformatics solutions. Dr. Jean-Noel Billaud will present a poster on the application of Ingenuity Pathway Analysis (IPA) on endometrioid endometrial carcinoma metastatic progression analysis.
Poster topic: Identification of potential immune targets in controlling endometrioid endometrial carcinoma metastatic progression

Author: Jean-Noel Billaud, Ph.D., Senior Principal Scientist – QIAGEN Bioinformatics

Topic category: Tumor Immunology

Date: Sunday, May 14

Time: 2.30 p.m. – 5.00 p.m.

In addition to our advanced bioinformatics solutions, QIAGEN also provides a broad range of assay technologies for immunological research, enabling analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. Visit QIAGEN’s immunology research portal here.

We look forward to seeing you at Immunology 2017 in D.C. on May 12–16!

 

The Society of Toxicology 55th Annual Meeting and ToxExpo will be held on March 13–17, 2016, in New Orleans, Louisiana.

You are welcome to visit us at booth #641 and at the poster board where Stuart Tugendreich will be presenting on "Functional and molecular responses to inhalation of MWCNT from the perspective of occupationally-relevant depositions".

Poster Abstract

Functional and molecular responses to inhalation of MWCNT from the perspective of occupationally-relevant depositions
3485: Poster Board - P175
Thursday, March 17, 9:30 a.m. – 12:45 p.m. 

Speaker: Stuart Tugendreich

In order to assess the toxicity response to occupationally-relevant depositions of multi-walled carbon nanotube (MWCNT), a dose- and time-dependent 4-week inhalation exposure to MWNCT (Mitsui-7) was initiated to represent a worker exposed to 76, 7.6 and 0.76 years at average inhalable workplace concentrations of 10.6 µg/m3. Mice were sacrificed at 0, 28, and 84 d post-exposure with lung, liver, and aorta collected for microarray-based gene expression profiling analyzed in conjunction with alterations in lavage proteins, alveolar macrophage function, histopathology, extrathoracic translocation, and systemic effects. Differentially expressed genes, upstream transcriptional regulators, and responses corresponding to inflammation/immune function and pathological changes (e.g. fibrosis) were persistent in the high dose but transient in the middle dose. The responses reflected the 58 lavage proteins measured and morphometric analysis of alveolar fibrosis which was increased in the high dose only. Similarly, isolated alveolar macrophages challenged with LPS (1 ug/ml) ex vivo enhanced cytokine production that was sustained in the high dose but transient in the middle dose. At all three doses, MWCNT translocated to the kidney and liver indicating a likely dependence on physicochemical properties. Analysis of systemic effects showed minimal to no changes in liver or aorta transcriptomics, 58 analyzed plasma proteins, or liver and renal histopathology. Plasma from only the high dose group increased adhesion molecule expression in primary endothelial cells. In summary, induced molecular mechanisms, histopathological changes, and systemic effects occur primarily at depositions (or dose rates) predicted to be significantly higher than expected in average workplace exposure scenarios.

More information about the SOT Annual Meeting and ToxExpo

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