Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


2D images as the new tool for cancer prevention


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.

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 Gentle sensors for diagnosing brain disorders
29.09.2016 | King Abdullah University of Science and Technology

nachricht New imaging technique in Alzheimer’s disease - opens up possibilities for new drug development
28.09.2016 | Lund University

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>