High Serum miR-361-3p Predicts Early Postdischarge Infections after Autologous Stem Cell Transplantation

Abstract

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is currently the backbone of the treatment of multiple myeloma (MM) and relapsed and refractory lymphomas. Notably, infections contribute to over 25% of fatalities among AHSCT recipients within the initial 100 days following the procedure. In this study, we aimed to evaluate three selected miRNAs: hsa-miR-155-5p, hsa-miR-320c, and hsa-miR-361-3p, in identifying AHSCT recipients at high risk of infectious events up to 100 days post-transplantation after discharge.

Materials and methods: The study group consisted of 58 patients (43 with MM, 15 with lymphoma) treated with AHSCT. Blood samples were collected from all patients at the same time point: on day +14 after transplantation.

Results: Fifteen patients (25.9%) experienced infectious complications after post-transplant discharge within the initial +100 days post-transplantation. The median time to infection onset was 44 days (interquartile range, 25-78). Four patients required hospitalization due to severe infection. High expression of hsa-miR-361-3p (fold change [FC], 1.79; P=0.0139) in the patients experiencing infectious complications and overexpression of hsa-miR-320c (FC, 2.14; P<0.0001) in patients requiring hospitalization were observed. In the multivariate model, both lymphoma diagnosis (odds ratio [OR], 6.88; 95% confidence interval [CI], 1.55-30.56; P=0.0112) and high expression of hsa-miR-361-3p (OR, 3.00; 95% CI, 1.40-6.41; P=0.0047) were independent factors associated with post-discharge infectious complications occurrence. Our model in 10-fold cross-validation preserved its diagnostic potential with an area under the receiver operating characteristic curve of 0.78 (95% CI, 0.64-0.92).

Conclusion: Elevated serum hsa-miR-361-3p emerges as a promising biomarker for identifying patients at risk of infection during the early post-discharge period, potentially offering optimization of the prophylactic use of antimicrobial agents tailored to the specific risk profile of each AHSCT recipient.

Keywords: AHSCT; Infection; miR-320c; miR-361-3p; miRNA.

Figure 1. Comparison of miRNAs expression between patients with (A,B,C) infectious complications and (D,E,F) required hospitalization.

Asterisks denote the significance level: ^aP≤0.05; ^bP≤0.0001. ns, not significant.

Figure 2. ROC curve of logistic regression model after 10-fold cross validation predicting infectious complications occurrence (AUC, 0.78; 95% CI, 0.64–0.916; P=0.0001).

ROC, receiver operating characteristics; AUC, area under the curve; CI, confidence interval.

Figure 3. KEGG pathway analysis (A) and target prediction analysis (B) of miRNAs differentially expressed in AHSCT recipients experiencing post-discharge infectious events- hsa-miR-361-3p and hsa-miR-320c. On panel B, genes involved in selected KEGG pathways were annotated: Herpes simplex infection (yellow color: CYCS, SRSF7, TRAF1, TRAF3, TNFSF14), TGF-beta signaling pathway (orange color: THBS1, THBS2, ACVR2B, RHOA), Wnt signaling pathway (green color: AXIN1, APC2, NFATC3, VANGL2, WNT10A, RHOA), T-cell receptor signaling pathway (red color: RHOA, GRAP2, PAK4, NFATC3).

KEGG, Kyoto Encyclopedia of Genes and Genomes.