Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2D images as the new tool for cancer prevention

01.12.2014

Portuguese researchers have developed a new method, which from images of a protein in a population of cells quantifies its distribution (how much there is, and where in the cell) for that population. The discovery by researchers João Sanches, Raquel Seruca and colleagues has important medical implications since the cellular location of a protein is directly linked to its function.

This was clear when the new algorithm was tested on cells with mutated e-cadherin (a tumour suppressor protein) where it identified the mutations that produced malfunctioning e-cadherin that causes human diffuse gastric cancer (HDGC), effectively pinpointing the patients at risk of the disease.


2D images identify gastric cancer-prone mutations

The result is particularly important because HDGC is asymptomatic and, at the moment, its early detection is not reliable what means that the disease still has extremely high mortality. The new algorithm with its ability to identify patients at high risk, hopefully, will change that.

The study, out in the European Journal of Human Genetics, is a collaboration between João Sanches from the Institute for Systems and Robotics and Department of Bioengineering from the Instituto Superior Técnico at the Technical University of Lisbon that developed the algorithm, and the group of Raquel Seruca from the Department of Cancer Genetics of IPATIMUP - Institute of Molecular Pathology and Immunology at the University of Porto that works in cancer.

Gastric cancer is the 4th most common cause of cancer in the world, and hereditary diffuse gastric cancer (HDGC) makes up to 3% of all cases. Although not very frequent, the disease is hugely problematic for clinicians because of its high mortality, which is the result of several issues.

First, the fact that HDGC is caused by functional abnormalities/mutations in e-cadherin, an adhesion protein of epithelial cells (those covering the surfaces and inside of the body). E-cadherin holds epithelial cells together by lying across the cell membrane, one end attached to e-cadherins from neighbouring cells and the other to the skeleton of the epithelial cell.

When e-cadherin stops working, the cells become loose. In the case of HDGC, this means that there is no solid tumour, but, instead, a loose layer of cancerous cells, which easily move spreading the disease and making its control impossible unless detection occurs early. This is also why e-cadherin is known as an important tumour suppressor molecule.

The second problem when trying to control the disease is the difficulty of spotting HDGC early. In fact its initial symptoms are very non-specific (stomach acidity and burping for example), so easy to miss. And without clear symptomology, early detection relies on searching gastric cells for lack of e-cadherin on the membrane (a malfunctioning e-cadherin also leaves the membrane to go inside the cell to be destroyed) with results that are not always reliable.

As consequence there has been a major effort to improve HDGC detection, and it is here that Sanches’ algorithm steps in. This new method has many advantages - it is semi-automated what allows, on one hand, the human operators to resort to their experience to choose the more representative cells, and on the other to rely on the computer to normalise results from cells with very different sizes and shapes, and work even with very heterogeneous cell populations. Resorting to images assured that the cells were hardly altered. All of these secured that the results were accurate and representative.

But how did it actually work? The software was designed to compute data from fluorescence images of the protein in a cell population, to generate “maps” of the protein distribution in that population. From these, it constructed 2D virtual images of a “typical cell” in that population, and it also calculated a new parameter called maximum mean ratio (MMR), which quantifies the sharpness of the protein fluorescence peak (so effectively measures the protein quantity). In HDGC experiments, a high MMR meant that e-cadherin has high expression by the membrane (as it should), and low levels inside of the cell

To see if this data could be used to improve the clinical management of HDGC, next, the researchers used the algorithm to compare cells with working e-cadherins, with those carrying mutations that made the protein non-functional/useless (so cancer prone). The idea was, that since normal e-cadherin is on the membrane and its malfunctioning form moves inside the cell to be destroyed, the new algorithm, by giving e-cadherin location, should be able to identify the individuals at risk of HDGC.

And in fact, after constructing 2D images of the two types of cells, the distinction was clear. While normal cells (or those with neutral/innocuous mutations) produced an image of a fluorescence circle with a clear centre (which represented the absence of protein inside the cell), those with malfunctioning e-cadherin (that can lead to HDGC) showed a full fluorescence circle (the fluorescence in the centre represented e-cadherin inside cell).

Additionally, these last cells had much lower MMR than normal, meaning less e-cadherin by the membrane and, in consequence, a weaker cell-to-cell adhesion what agreed with their propensity to cancer. “Our algorithm was not only able to pinpoint the protein location, but also to quantify it in each cellular compartment. While the MMR value gave us the protein dispersion.” - says Seruca

In conclusion, with a combination of 2D images and quantitative “maps” should now be much easier for researchers (and in the future clinicians) to quickly and reliably identify those individuals with mutations that lead e-cadherin to lose its function, and who, as result, are prone to develop HDGC, and who should be put under close monitoring for early signs of disease.

“Our algorithm can now be used as a complementary approach to evaluate the pathogenicity of E-cadherin.”- says Seruca - “Moreover, it can be applied to a wide range of proteins and, more importantly, to diseases characterized by aberrant protein expression or trafficking deregulation. “

And although the study has focused on HDGC, e-cadherin mutations are known to be involved in a variety of other cancers including breast, colorectal, thyroid and ovarian so these new results could also be applied to them.


http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2014240a.html

Full bibliographic information

European Journal of Human Genetics (2014), 1–8
Quantification of mutant E-cadherin using bioimaging analysis of in situ fluorescence microscopy. A new approach to CDH1 missense variants
João Miguel Sanches, Joana Figueiredo, Martina Fonseca1, Cecília Durães, Soraia Melo, Sofia Esménio and Raquel Seruca*

Catarina Amorim | AlphaGalileo

More articles from Medical Engineering:

nachricht Wireless power can drive tiny electronic devices in the GI tract
28.04.2017 | Brigham and Women's Hospital

nachricht Artificial intelligence may help diagnose tuberculosis in remote areas
25.04.2017 | Radiological Society of North America

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>