Contributions
Abstract: EP1296
Type: E-Poster Presentation
Session title: Stem cell transplantation - Experimental
Background
Chronic graft versus host disease (cGVHD) is the most common long-term complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), associated with increased mortality, high disease burden and significant reduced quality of life for patients. The pathophysiology behind the disease is complex and insufficiently understood. The last decade has brought interest to single stranded noncoding RNA molecules; microRNAs (miRNAs), as important components in the pathophysiological process of cGVHD. However, their role in development of cGVHD and the possibilities of utilizing them as biomarkers are mainly unknown.
Aims
The objectives of this study were to investigate a broad specter of serum miRNAs from allografted patients and investigate associations between individual miRNAs and miRNA profiles, and cGVHD and their use as potential biomarkers for patients with cGVHD.
Methods
The study included 79 consecutively allotransplanted adults, 46 men and 33 women with median age of 49 years (range 15-71 years). Patients were transplanted with peripheral blood stem cells (PBSCs) derived from human leukocyte antigen (HLA)-matched family donors. Serum samples were obtained one year after the allo-HSCT, and stored under standard procedures before serum miRNA-seq analysis was performed using QIAGEN CLC Genomics Server v20.0.4 for all 79 patients.
Results
50 of the 79 patients (63%) had signs of cGVHD at the one-year post-allo-HSCT control. The affected organ systems were; liver/bile duct (n=26), skin (n=22), gastrointestinal tract (n=21), eyes (n=21), mouth (n=17), lungs (n=3), urogenital tract (n=3), and musculoskeletal (n=1). miRNA-seq analysis revealed 1380 different miRNAs detected for at least one patient, while 233 miRNAs (17%) were detected in more than 70 patients. After corrections for age and by searching for discriminative miRNAs, we identified 29 microRNAs that differed significantly between patients with and without cGVHD (p-values <0.02), and 21 of these 29 miRNAs were detected for ≥ 70 of the patients. Among these 21 miRNAs, 12 were in particular differentially expressed (p-values <0.007). The results indicate that the difference in serum miRNA profiles between the two groups was considerable, and cGVHD appeared to have a profound impact on circulating miRNAs. Furthermore, five distinct miRNAs; miR-365-3p, miR-148-3p, miR-122-3p, miR-378-3p, and miR-192-5p, were found to be highly associated with cGVHD in our analysis, and validated by receiver operating characteristics (ROC) analysis. Based on these five miRNAs, we developed a miRNA signature which by bioinformatic approaches and linear regression model utterly improved our prediction model for cGVHD. Finally, literature reviews support the association between individual microRNAs and cGVHD and inflammation.
Conclusion
To conclude, the present miRNA profiling study was conducted to identify serum miRNA signatures associated with cGVHD, and our observations suggest that cGVHD is associated with significant and profound alterations in miRNA serum profiles. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings and investigate the potential diagnostic and prognostic impact of circulating miRNAs among allo-HSCT recipients.
Keyword(s): Allogeneic stem cell transplant, Chronic graft-versus-host
Abstract: EP1296
Type: E-Poster Presentation
Session title: Stem cell transplantation - Experimental
Background
Chronic graft versus host disease (cGVHD) is the most common long-term complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), associated with increased mortality, high disease burden and significant reduced quality of life for patients. The pathophysiology behind the disease is complex and insufficiently understood. The last decade has brought interest to single stranded noncoding RNA molecules; microRNAs (miRNAs), as important components in the pathophysiological process of cGVHD. However, their role in development of cGVHD and the possibilities of utilizing them as biomarkers are mainly unknown.
Aims
The objectives of this study were to investigate a broad specter of serum miRNAs from allografted patients and investigate associations between individual miRNAs and miRNA profiles, and cGVHD and their use as potential biomarkers for patients with cGVHD.
Methods
The study included 79 consecutively allotransplanted adults, 46 men and 33 women with median age of 49 years (range 15-71 years). Patients were transplanted with peripheral blood stem cells (PBSCs) derived from human leukocyte antigen (HLA)-matched family donors. Serum samples were obtained one year after the allo-HSCT, and stored under standard procedures before serum miRNA-seq analysis was performed using QIAGEN CLC Genomics Server v20.0.4 for all 79 patients.
Results
50 of the 79 patients (63%) had signs of cGVHD at the one-year post-allo-HSCT control. The affected organ systems were; liver/bile duct (n=26), skin (n=22), gastrointestinal tract (n=21), eyes (n=21), mouth (n=17), lungs (n=3), urogenital tract (n=3), and musculoskeletal (n=1). miRNA-seq analysis revealed 1380 different miRNAs detected for at least one patient, while 233 miRNAs (17%) were detected in more than 70 patients. After corrections for age and by searching for discriminative miRNAs, we identified 29 microRNAs that differed significantly between patients with and without cGVHD (p-values <0.02), and 21 of these 29 miRNAs were detected for ≥ 70 of the patients. Among these 21 miRNAs, 12 were in particular differentially expressed (p-values <0.007). The results indicate that the difference in serum miRNA profiles between the two groups was considerable, and cGVHD appeared to have a profound impact on circulating miRNAs. Furthermore, five distinct miRNAs; miR-365-3p, miR-148-3p, miR-122-3p, miR-378-3p, and miR-192-5p, were found to be highly associated with cGVHD in our analysis, and validated by receiver operating characteristics (ROC) analysis. Based on these five miRNAs, we developed a miRNA signature which by bioinformatic approaches and linear regression model utterly improved our prediction model for cGVHD. Finally, literature reviews support the association between individual microRNAs and cGVHD and inflammation.
Conclusion
To conclude, the present miRNA profiling study was conducted to identify serum miRNA signatures associated with cGVHD, and our observations suggest that cGVHD is associated with significant and profound alterations in miRNA serum profiles. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings and investigate the potential diagnostic and prognostic impact of circulating miRNAs among allo-HSCT recipients.
Keyword(s): Allogeneic stem cell transplant, Chronic graft-versus-host