The level and integrity of plasma circulating cell-free DNA in patients with primary multiple myeloma

Abstract

Background: To evaluate the clinical research related to the level and integrity of circulating free DNA (cfDNA) in the plasma of patients with multiple myeloma (MM). Methods:The plasma samples of 56 patients with newly diagnosed MM and 60 healthy volunteers were collected. ALU247 fragment and ALU115 fragment were used as target genes, and quantitative polymerase chain reaction (qPCR) was used to assess the plasma of the patient and healthy control groups. The cfDNA level in MM was analyzed, and the ALU247/ALU115 ratio was used to calculate the integrity of cfDNA.The correlation between the cfDNA level and integrity and the clinical characteristics of patients with primary MM was analyzed, and their value in efficacy monitoring and prognostic evaluation was evaluated. Results:The plasma concentrations of ALU247 and ALU115 and the integrity of cfDNA in patients with primary MM were significantly higher than those in the healthy controls (P<0.05). The ALU247 fragment concentration was markedly correlated with the Durie-Salmon (D-S), International Staging System (ISS), and Revised-International Staging System (R-ISS) stages (P<0.05). After three courses of induction chemotherapy, the levels of ALU247, ALU115, and cfDNA integrity in both groups were lower than those before chemotherapy (P<0.05). Patients with curative effects of CR, sCR, and VGPR were classified into the ≥ very good partial response (VGPR) group (n=38), while those with curative effects of PR and SD were allocated into the <VGPR group (n=18). In addition, after chemotherapy, the levels of ALU247, ALU115, and cfDNA integrity of patients in the ≥ VGPR group were significantly lower than those in the < VGPR group (P<0.05). The follow-up results showed that the progression-free survival (PFS) of MM patients with low ALU247 expression was considerably longer than that of MM patients with high ALU247 expression (33.59±1.15 vs. 27.31±2.16, P<0.05).Conclusions: CfDNA levels were significantly elevated in MM patients, and the ALU247 fragment concentration was remarkably correlated with multiple clinical features and had important clinical value for efficacy monitoring and prognostic assessment.

Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer

“…This means that the cfDNA in PJ may potentially be contaminated with high concentrations of genomic DNA (as a result of cell decay during collection). Conversely, the higher Alu247/Alu115 ratio in PJ may be due to its close relation with PC and may be a measure of cell necrosis (rather than apoptosis), as necrosis produces longer cfDNA fragments [14][15][16][17]. If so, the Alu247/Alu115 ratio in PJ may be a measure of tumor volume and response to therapy.…”

The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples

“…Each step involves numerous conditions or details, and the variables interact with each other. Moreover, many studies inadequately describe the preanalytical variables for cfDNA analysis in their Materials and Methods sections ( Campbell et al, 2015 ; Wolf-Doty et al, 2021 ; Shen et al, 2022 ), leading to questionable credibility of analytical results and inefficiency in method verification. Diao et al surveyed the quality assurance (the questionnaire included preanalysis, postanalysis and performance validation for mNGS) of metagenomic next-generation sequencing (mNGS) used for detecting microbial cfDNA in blood samples across 80 laboratories in China and found significant variation in the mNGS workflow among the laboratories ( Diao et al, 2022 ).…”