Researchers from the Karolinska Institutet in Sweden have identified four specific genes in kidney cancer cells that may help predict the risk of tumour’s spreading and patients’ chances of survival.
Clear-cell kidney cancer is the most common form of kidney cancer in adults. If the tumour does not spread beyond the kidneys, a patient’s chances of survival are usually favourable. However, if cancer spreads to the skeleton, which occurs in around one-third of patients, the five-year survival rate is only 10%.
Immunotherapy, sometimes referred to as checkpoint inhibitors, is an important treatment for patients with clear-cell kidney cancer. Unfortunately, it is common for cancer cells to develop resistance to the treatment. Scientists believe this may be due to factors in the environment around the cancer cells, known as the tumour microenvironment.
Using genetic sequencing to kidney cancer
In this study, researchers from Karolinska Institutet worked alongside clinicians at Massachusetts General Hospital to analyse samples from nine kidney cancer patients. The researchers collected tumour tissue and nearby normal kidney tissue from each patient. The cells were studied through single-cell analysis; a sequencing technique which makes it possible to study each cell in the tissue and the gene expression. This enabled the research team to identify which genes were active in individual cells.
Details of the preclinical study have been published in the journal Nature Communications.
“This could potentially become a tool to gain a better understanding of the course of the disease at an early stage. Patients with a cancer profile with a high probability of spreading could then be monitored more closely, to quickly detect and treat any growth of the tumour,” said Ninib Baryawno, senior researcher at the Department of Women’s and Children’s Health, Karolinska Institutet, and the study’s last author.
Through their analysis, the researchers found a genetic signature of four specific genes that is predictive of whether a tumour will spread to the skeleton. Simultaneous overexpression of the genes SAA1, SAA2, APOL1 and MET suggest that a patient has a greater chance of kidney cancer spreading to the skeleton and therefore a lower chance of survival. This association was confirmed when the researchers examined tumour cells from bone metastases in seven patients with clear-cell kidney cancer.
Findings may lead to drug development
The study has shown that the microenvironment of the tumour inhibits the immune system, The researchers have suggested several possible targets for drugs to investigate further. These were identified through computer simulations of cell interactions.
The findings have provided important knowledge about the relationship between kidney cancer cells and their microenvironment.
“We hope that our results will contribute to further investigations of factors that affect the tumour microenvironment, which can ultimately provide new ways to treat relapse and the spread of cancer. For us, the next step is to study how metastases in the bone marrow and the skeleton differ from the local tumour in the kidney but also how the bone marrow in patients with kidney cancer metastases in the skeleton differs from healthy bone marrow,” said Adele Alchahin, PhD student at the Department of Women’s and Children’s Health, Karolinska Institutet and co-author of the study.
“We hope that it can help us answer the question as to why immunotherapy does not work in some kidney cancer patients,” she added.
