On September 30, 2020, a group of Skoltech scientists led by Skoltech and Moscow State University professor Olga Dontsova announced the discovery of a novel liver-specific, non-coding RNA. The researchers tracked RNA levels in a healthy liver and one affected by carcinogenesis and suggested that RNA be used as a biomarker, creating a new panel of potential biomarkers for the postoperative diagnosis of various liver cancers.

The findings were published in the Journal of Cancer Research and Clinical Oncology. The study was funded by the Russian Science Foundation (RSF).

Tumor markers help doctors determine if a patient has cancer. One substance that can be used as a tumor marker at different concentrations is non-coding RNA, i.e. RNA molecules that do not encode proteins but play an important role in the regulation of cell activity. Non-coding RNA occurs in all somatic cells and in certain organs and tissues.

A team of Skoltech scientists discovered a previously undescribed non-coding RNA in the liver that can be used as a biomarker. They named the new molecule HELIS (Healthy Liver Specific) because, unlike classical tumor markers, which are indicators of disease, it acts as a healthy liver biomarker and can even be described as an anti-tumor marker.

Olga Burenina, a research scientist at the Skoltech Center for Life Sciences (CLS) and lead author of the paper, believes this can be an advantage, “Many classic tumor markers do not always show up in the case of cancer or may have elevated levels due to non-cancer-related diseases including cirrhosis or hepatitis in the case of the liver. The markers of the ‘healthy liver’ may be more revealing. If there is a malfunction in the cancer cells and HELIS is no longer produced as it should be, the problem may not be as easy to resolve.”

Other organizations involved in the joint research were the Carcinogenesis Research Institute at the Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation and the Petrovsky National Research Center for Surgery, which provided post-operative samples for six types of liver tumors.

The scientists were successful in demonstrating that HELIS levels fell significantly below normal in all samples, while they completely disappeared in several malignant tumor types. The scientists then investigated the behavior of some known non-coding RNAs in these samples and selected three further potential tumor markers. As a result, they were given a panel of four biomarkers that are expressed differently in different types of liver cancer and, importantly, help distinguish between benign and malignant tumors.

“Currently there is no single good diagnostic marker for liver cancer, so doctors make the diagnosis mainly on the basis of ultrasound or computerized tomography tests and remove the entire tumor by surgery, regardless of the type of cancer suspected. As biopsy is rarely performed, the final diagnosis is based on the histological findings, which are available after 10 to 14 days,” explained Olga Burenina.

The new panel of biomarkers can be used for rapid pre-diagnosis on the basis of post-operative liver tumor samples and for additional analysis in unclear clinical cases.