Biomarker for most common cancer in young men confirmed microbiologystudy

Cornell researchers have confirmed that a previously identified biomarker for detecting the presence of malignant testicular germ cell tumors—the most common solid cancers in young men—has the potential to improve patient outcomes through early detection, possibly even prenatally.

The study in mice, published in Scientific Reports, describes how certain microRNAs (miRNA), which regulate genes by turning off their ability to express proteins, are very specific to testicular germ cell cancer and therefore serve as a reliable biomarker. The miRNAs identified in mice also have a homolog in humans.

“In cancer diagnosis, there’s a big push to go toward less invasive approaches, often referred to as liquid biopsies,” said Robert Weiss, professor of molecular genetics in the Department of Biomedical Sciences in the College of Veterinary Medicine (CVM). “From a blood sample, one can monitor for the presence of disease, early detection, or relapse from surgery, so this is a terrific example of the advancement of that technology.”

Malignant testicular germ cell tumors are the most common cancers diagnosed in males ages 15 to 39 in the U.S., though incidence has increased by almost 40% in the last 50 years. At the same time, they are the most responsive tumors to conventional chemotherapy, leading to a five-year survival rate of 95%. Evidence indicates that the tumors originate in utero during embryonic development and can progress to become an invasive cancer, most typically after puberty.

The cancer contains pluripotent cancer stem cells, which have the ability to differentiate into various cancer cell types. In the study, the researchers used an existing mouse model, previously developed by Weiss and colleagues, which allowed them to target and control testicular germ cell tumor development.

The system also allowed them to culture tumor cells in the lab and force them to differentiate, so they lose their pluripotent stem cell features. By doing so, they could compare the original, undifferentiated pluripotent stem cells with ones that had progressed to differentiated, more specialized cells.

The study was motivated by clinical studies in humans that suggested miRNAs in blood serum could serve as a biomarker. Through the mouse model, the researchers found that a cluster of miRNAs, labeled miRNA 290-295 in mice, were exclusively expressed and secreted by undifferentiated testicular cancer cells. These correspond to the miRNA 371-373 cluster in humans.

The mouse model revealed that the miRNAs are exclusive to these testicular cancers, and couldn’t be detected if a mouse had a mammary tumor instead of a malignant testicular cancer, or if a testicular tumor was benign. This specificity makes these miRNAs very accurate biomarkers.

The researchers also identified the genes that the miRNAs target and down regulate. “If you look at the functions of those genes, they regulate cancer-related processes, cell cycle and apoptosis [cell death],” Weiss said.

The study, Weiss said, points to the importance of the mouse model as an authentic model of human disease, which allows for research that isn’t possible in humans.

The findings open the door for further study, he said. The study’s authors plan to investigate the functions of these miRNAs to better understand the genes they affect and what those genes do.

“If our expectation is confirmed that these miRNAs do have important functional roles,” Weiss said, “then they provide another step as therapeutic targets that we could go after to block tumor growth or metastasis.”