Genetic characteristics indicate the prognosis of kidney cancer

In kidney cancer patients, the activity of four specific genes in the cancer cells appears to predict the risk of tumor spread and the patient's chances of
survival.

"This has the potential to be a tool to better understand the course of
the disease at an early stage.
" Patients with a high likelihood of tumor spread can then be monitored more closely to quickly detect and treat any tumor growth," said
Ninib Baryawno, senior researcher at the Department of Women's and Children's Health at Karolinska Institutet and the study's last author.

Clear cell kidney cancer is the most common kidney cancer
in adults.
If the tumor is localized to the kidneys, the prognosis is usually good, but if the tumor spreads to the bones, it occurs in about a third of patients, with a 5-year survival rate of only about
10%.

Immunotherapy, known as checkpoint inhibitors, has become an important treatment for
patients with clear cell kidney cancer in recent years.
But it is common for cancer cells to develop resistance to treatment, which may be due in part to factors in the environment surrounding cancer cells, the so-called tumor microenvironment
.

In the current study, the researchers examined samples
from 9 patients with clear cell kidney cancer.
The study was conducted in collaboration between researchers at the Karolinska Institutet, clinicians at Massachusetts General Hospital who recruited patients, and computational scientists from Harvard Medical School in Boston
.

Both tumor tissue and nearby normal kidney tissue are collected from the same patient to be able to make matching comparisons and control for variation
between individuals.
Cells are analyzed using single cells; A sequencing technique that studies every cell and gene expression in a tissue, that is, which genes are active
in individual cells.

In two patients, the researchers also compared primary tumor tissue from the kidneys and tissue
from bone metastases.

The study shows that a genetic trait made up of four specific genes can predict whether a tumor will spread to the bone and whether it will survive or
not.
Simultaneous overexpression of these genes (SAA1, SAA2, APOL1, and MET) indicates that patients are at greater risk of developing tumor spread and poor survival outcomes
.

When the researchers examined bone metastatic tumor cells in 7 patients with metastatic clear cell kidney cancer, they also confirmed the association
of genetic characteristics with the risk of spread.

In addition, the study shows that the tumor's microenvironment suppresses the immune system, and the researchers have proposed several possible drug targets that may merit further study
.
These are determined by computer simulations of cellular interactions
.

The researchers say the study provides important biological insight
into the interactions between tumor cells and their microenvironment in clear cell kidney cancer.

"We hope that our results will contribute to further studies of the factors that influence the tumor microenvironment, which could eventually provide new ways to
treat cancer recurrence and spread.
" For us, the next step is to investigate the difference between bone marrow and bone metastases and local tumors in the kidneys, and the bone marrow from
healthy bone marrow in patients with bone metastases kidney cancer.
We hope it will help us answer the question of why immunotherapy doesn't work for some kidney cancer patients," said Adele Alchahin, a doctoral student in the Department of Women's and Children's Health at Karolinska Institutet and one of
the study's first authors.

KI researchers involved in the publication say there is no potential conflict of
interest.
Other authors are associated with a variety of pharmaceutical and biotechnology companies in the form of founding and consulting commitments
.
See the scientific article
for more information.