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

Qian Shen; Haiyan Cen; Jing Jiang; Zhirong Cong; Ying Zhou; Xiaoxiao Huang; Li Zhu; Qi Jiang; Chenqi Xue

doi:10.21037/tcr-22-2416

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

Transl Cancer Res. 2022 Nov;11(11):4137-4147. doi: 10.21037/tcr-22-2416.

Authors

Qian Shen^#¹, Haiyan Cen^#², Jing Jiang³, Zhirong Cong¹, Ying Zhou¹, Xiaoxiao Huang⁴, Li Zhu¹, Qi Jiang¹, Chenqi Xue⁵

Affiliations

¹ Department of Hematology and Lymphoma, Tumor Hospital Affiliated to Nantong University, Nantong, China.
² Department of Hematology, Affiliated Hospital of Nantong University & Nantong Geriatric Rehabilitation Hospital, Nantong, China.
³ Department of Radiology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
⁴ Department of Laboratory Medicine, Tumor Hospital Affiliated to Nantong University, Nantong, China.
⁵ Department of Interventional Radiology, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.

^# Contributed equally.

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.

Keywords: Primary multiple myeloma (primary MM); circulating free DNA (cfDNA); efficacy monitoring; prognosis assessment.