In a new study, RNA patterns related to hepatocellular carcinoma (HCC) and multiple myeloma (MM) showed potential to help distinguish between cancerous and precancerous states. The results of this study were reported in the journal NPJ Precision Oncology.

The researchers who conducted the study explained in their report that many studies have examined early detection of cancer based on distinguishing between cancerous and noncancerous, or control, conditions. However, those regarding discrimination of cancerous from precancerous states have been more limited. The researchers explained there are potential benefits to patients in identification of precancerous states, and currently diagnosis of cancer often utilizes invasive or expensive techniques. They considered an unmet clinical need to be a blood test that can distinguish precancerous conditions to aid in management.

In this study, the researchers developed models using cell-free messenger RNA (mRNA) profiling to distinguish between cancerous, precancerous, and noncancerous states related to HCC and MM. Both HCC and MM are often preceded by precancerous states, such as liver cirrhosis and monoclonal gammopathy of undetermined significance (MGUS), respectively. For model development, the researchers sequenced cell-free mRNA obtained from the plasma of 8 patients with HCC, 10 patients with MM, 12 patients with liver cirrhosis, 12 patients with MGUS, and 20 donors without cancer who were considered to represent the noncancerous state.

Continue Reading

The researchers analyzed cell-free mRNA profiles using different classification algorithms to develop models for distinguishing between cancerous and noncancerous states. Top genes identified for comparisons mostly reflected liver-specific genes for HCC or genes with high expression in the bone marrow for MM. Expression levels of many of these genetic biomarkers for either HCC or MM tended to gradually increase from noncancerous, through precancerous, to cancerous states.

Cell-free mRNA profiling seemed able to help distinguish both HCC and MM from their precancerous and noncancerous states based on tests of accuracy across models. An analysis of a model including MM, MGUS, and noncancerous states showed an accuracy of 86.8%. An analysis of a similar model with HCC, liver cirrhosis, and noncancerous states had an accuracy of 90.6%.

Additionally, a test to validate the biomarkers used in 1 model for distinguishing cancerous and noncancerous states, using samples from a different population, showed a value of 0.86 in an area-under-the-curve analysis. However, the researchers indicated that results related to distinguishing precancerous states, while promising, should undergo further validation. The researchers also noted that the stability of cell-free RNA, and the biological origins of biomarkers used in this study, have not been fully evaluated.

“In summary, we report a proof of principle that global profiling of cell-free mRNA has the potential to establish a platform for longitudinal monitoring of disease progression across both solid and hematologic cancers,” the researchers concluded in their report.


Roskams-Hieter B, Kim HJ, Anur P, et al. Plasma cell-free RNA profiling distinguishes cancers from premalignant conditions in solid and hematologic malignancies. NPJ Precis Oncol. 2022;6(1):28. doi:10.1038/s41698-022-00270-y