Spanish Cancer Company Universal Dx to Commercialize Methylation Method for Lung Cancer Detection
NEW YORK - Spanish cancer research firm Universal Diagnostics is gearing up to commercialize a liquid biopsy test that applies methylation biomarkers to detect lung cancer, based on data presented at the International Association for the Study of Lung Cancer 2020 World Conference for Lung Cancer (WCLC) last month.
The Seville-based firm also expects to release clinical data on its next generation sequencing-based colorectal cancer (CRC) assay later this year.
Christian Hense, chief operating officer of Universal Dx, said that the method`s workflow begins by collecting about 4ml of plasma from 8ml to 10ml of a patient`s blood sample for cell-free DNA (cfDNA) extraction.
After Universal Dx performs a series of processing steps to enrich for targets of interest, Hense said that the team then uses methylation-sensitive restriction enzyme qPCR, or MSRE-qPCR, which applies enzymes that recognize specific "4-nucleotide DNA motifs containing CpG sequences" and digest the unmethylated cytosines.
According to Hense, a methyl group at the fifth position of cytosine renders the group impossible to be digested by the enzymes, and "after successful incubation of DNA with MRSEs and PCR amplification, only methylated DNA results in a detectable PCR result."
Universal Dx then applies its proprietary bioinformatics pipeline to the PCR data to identify patients with potential early-stage lung cancers.
In a study abstract presented at WCLC, Universal Dx and its academic collaborators collected plasma samples from 37 patients with stages
l-IV lung cancer, including 11 adenocarcinoma, 10 squamous cell carcinoma, 11 small cell lung cancer (SCLC), and five rare lung cancer subtypes (large cell, carcinoid tumors). The team also collected 71 asymptomatic age, gender, and smoking-history matching controls.
Applying MSRE-qPCR, the researchers built a 10-biomarker panel to identify the methylation status of tumor-derived cfDNA in the lung cancer patients.
The group found that the panel had an area under the curve of 85 percent, with a sensitivity of 73 percent and specificity of 90 percent. The panel also identified 82 percent of the adenocarcinoma, 80 percent of the squamous cell carcinoma, 73 percent of the SCLC, and 40 percent of the rare cancer subtypes as cancer patients.
In an email, Dennis Lo, director of the Li Ka Shing Institute of Health Sciences at the Chinese University of Hong Kong, noted the MSRE-qPCR tool indicates that methylation-based markers in cfDNA in blood "represent promising markers in cancer detection."
His team previously used a similar methylation-based approach to detect liver cancer and is now using a method that analyzes the presence of "jagged-ends" in cfDNA fragments to correlate with fetal and tumor-derived cfDNA.
"I think that it would be interesting to see a comparison between the pros and cons between such a restriction enzyme-based approach versus the more commonly used bisulfite-based approach," Lo said.
However, Lo, who is not affiliated with Universal Dx or with the development of its test, pointed out that the small sample size in the study is relatively low and will require future large-scale validation studies. In addition, he questioned "whether the specificity of 90 percent would be sufficient for clinical use."