Cancer occurs in individuals whose essential molecular mechanisms in cells are not functioning normally. To facilitate the understanding of these pathological activities, scientists have been relentlessly studying tumor cells at protein and Ribonucleic acid (RNA) levels. That’s because RNA are the messengers between our genes and the proteins that they code for and usually, cancer involves many different types of RNA.
New 3D imaging technique
Recently, researchers at Karolinska Institutet and Karolinska University Hospital in Sweden had developed a new way of examining intact, rather than sectioned human tumor samples in three-dimensional (3D) on a molecular level. This new technique requires tissues to be made transparent and stained with different kinds of RNA and proteins before digitizing into 3D images using an instrument called a light-sheet microscope. Researchers will then use an advanced image processing software to analyze these 3D images.
By doing so, location within a tumor where there are abnormal amounts of RNA and proteins shall be determined. Researchers will also be able to recognize individual cell in a tumor and how cell clusters or specific cell populations arrange themselves in relation to the tumor’s blood vessel structure. Known as DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), this new imaging technique facilitates an overall learning of cancer related mechanisms and permits a more accurate pathological diagnosis based on tumor tissues obtained from cancer patients.
For example, in one of the experiments, researchers were looking at the presence of “cancer stem cells” in a rather aggressive form of breast cancer by staining PROM1 RNA, a biomarker for the cancer stem cell. Cancer tumors tend to contain a minute number of cancer stem cells and they thoughts to play a crucial role in cancer formation. The DIIFCO method found small clusters of cancer stem cells in the tumor samples from patients diagnosed with breast cancer.
Using the technique to detect COVID-19
The project’s Principal Investigator and Professor at the Department of Medical Biochemistry and Biophysics Per Uhlén said, “for years, clinicians have used the labelling of specific proteins to diagnose tissue samples from tumors. Being able to specifically stain RNA in intact tumor samples opens up entirely new opportunities for clinical specimen diagnosis.”
Researchers are now able to use the DIIFCO method to study RNA and proteins at high resolution in all human tissue. They are also planning to use the method to study tissue samples of COVID-19 patients. The Polymerase Chain Reaction (PCR) is the standard test use for identifying individuals infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), the causative agent of COVID-19. Researchers will like to use DIIFCO to see where exactly in the tissue the viral RNA is.
“Ours is one of the few labs in the world able to study intact tissue samples from humans. This is particularly difficult when the tissue comes from elderly patients. I believe and hope that our method can provide important answers to where and how the new coronavirus attacks different organs” Professor Uhlén adds. The new technique and related findings were published in Nature Biomedical Engineering.