Can liquid biopsies successfully detect MSI and TMB, can they predict the response to immunotherapy?

An article published this month in the journal Clinical Cancer Research showed that a liquid biopsy could detect microsatellite instability (microsatellite instability, MSI) and two biomarkers, tumor mutation load (tumor daburden, TMB), associated with progression-free survival (PFS) of immunocheckpoint inhibitor therapymicrosatellites are repeated DNA sequences distributed along the genome in coded and non-coding regions, consisting of sequences of 1 to 6 bases in lengthThe repeatability of microsatellites makes them particularly sensitive to DNA mismatchesMSI is an inherited mutation state caused by DNA mismatch repair functional defects, characterized by the accumulation of microsatellite mutationsMSI is evidence of mismatch editing to repair a not functioning profileTMB refers to the number of non-sane mutations in somatic cells with an average of 1Mb base in the exon regionThe higher the Cancer Cell TMB, the more new antigens may be produced, so the higher the tumor's antigen immunogenicity, the more suitable for immunotherapyin this study, researchers attempted to assess the sensitivity and specificity of liquid biopsy methods developed based on individual genomic diagnosticsLiquid biopsy tests can cover a larger group of patients, such as patients with limited tissue acquisition or safety issues with additional surgical interventionsThe researchers developed a pan-cancer detection matrix containing 58 genes, then used a multifactor correction method and a new peak-finding algorithm to find the allele of MSI transcoding in the cell-free DNA (cfDNA) in the bloodIf it is determined that 20% or more of the gene sites have MSI, the sample is classified as MSI highfor MSI, the specificity of the liquid biopsy test is greater than 99% and the sensitivity is 78%For TMB, the specificity of the liquid biopsy test is greater than 99% and the sensitivity is 67%researchers found that IN patients being treated with immunocheckpoint inhibitors, MSI was directly detected in baseline cfDNA in patients with PFSHowever, the improvement in the overall survival rate did not meet the statistically significant criteria"Our data suggest that msI and TMB liquid biopsy analysis may be more predictive of immunotherapy response than archived tissue samples because it is both real-time and systemic, and addresses the inherent sampling bias of tissue biopsies," said Andrew Georgiadis, the first author of the"