High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation

Abstract

IntroductionAHSCT is the treatment of choice for newly diagnosed patients with transplant-eligible multiple myeloma (MM). However, considerable variability in response to autologous hematopoietic stem cell transplantation (AHSCT) results in only 50% of patients achieving complete response (CR) after AHSCT, which is directly associated with improved progression-free and overall survival (OS). In this study, we aimed to investigate the potential predictive role of selected serum miRNAs in MM patients who underwent AHSCT.Patients and methodsSerum expression level of 6 miRNAs: miR-221-3p, miR-15b-5p, miR-223-3p, miR-320c, miR-361-3p, and miR-150-5p was evaluated in 51 patients who underwent AHSCT. Blood samples were collected at two time points: before conditioning chemotherapy (T1) and fourteen days after transplant (+14) (T2).ResultsAll selected miRNAs significantly changed their expression level across the procedure- two were up-regulated after AHSCT: hsa-miR-320c (FC 1.42, p<0.0001) and hsa-miR-361-3p (FC 1.35, p=0.0168); four were down-regulated: hsa-miR-15b-5p (FC 0.53, p<0.0001), hsa-miR-221-3p (FC 0.78, p=0.0004), hsa-miR-223-3p (FC 0.74, p=0.0015) and hsa-miR-150-5p (FC 0.75, p=0.0080). Notably, before AHSCT, hsa-miR-223-3p was down-regulated in International Staging System (ISS) III patients (FC=0.76, p=0.0155), and hsa-miR-320c was up-regulated (FC=1.27, p=0.0470). These differences became non-significant after AHSCT. Eight (15.69%) patients achieved CR before AHSCT and 17 patients (33.33%) at +100 days after AHSCT. In multivariate logistic regression analysis, achievement of CR after induction and hsa-miR-223-3p at T1 were independent predictors of CR after AHSCT. In multivariate Cox regression analysis, hsa-miR-223-3p at T1 expression level was associated with prolonged OS (HR 0.06, 95%CI: 0.00 - 0.99, p=0.0488).ConclusionSerum expression of has-miR-223-3p is a predictor of CR and prolonged OS in MM patients undergoing AHSCT.

A low thrombospondin‐1 serum concentration is related to increased bacteremia risk in lymphoma patients treated with BeEAM/BEAM conditioning regimen and autologous stem cell transplantation

“…Our previous study demonstrated that small non‐coding RNA molecules, miRNAs, are significantly deregulated in serum during the AHSCT procedure 17,18 . According to bioinformatic analysis, conducted using miRNet 2.0 (http://www.mirnet.ca/ accessed July 16 2023), we found that six significantly deregulated miRNAs are associated with the gene THBS1 encoding the protein thrombospondin‐1 (Figure 1A) (Figure S1).…”

“…Our previous study demonstrated that small non-coding RNA molecules, miRNAs, are significantly deregulated in serum during the AHSCT procedure. 17,18 According to bioinformatic analysis, conducted using miRNet 2.0 (http://www.mirnet.ca/ accessed July 16 2023), we found that six significantly deregulated miRNAs are associated with the gene THBS1 encoding the protein thrombospondin-1 (Figure 1A) (Figure S1). 19 Combined with literature analysis regarding various THBS-1 influences on the immune system we assumed THBS-1 serum concentration may act as a biomarker of infectious complications ocurrence.…”

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

“…The focus on serum miRNAs stems from the clinical availability, reliability, and ease of introducing blood-based biomarker tests to clinical practice. Serum miRNAs, released into circulation by various cell types, including hematopoietic and non-hematopoietic cells, would thus provide a more comprehensive insight into the incipient complications and outcome predictions [49][50][51]. In addition, assessment of miR-122 in other populations, including allogeneic hematopoietic stem cell transplant recipients, would be exciting in the context of hepatic GvHD, as miR-122 was already reported to be up-regulated in sera of patients with chronic GvHD [52].…”