CIRCULATING PLASMA LONG NON-CODING RNA GAS5 AS NON-INVASIVE BIOMARKER IN MULTIPLE MYELOMA PATIENTS

Abstract

Background: Growth arrest specific 5 (GAS5) is a long non-coding RNA that has been reported as a prognostic biomarker in numerous malignancies. Clinical and prognostic significance of circulating plasma GAS5 expression in patients with multiple myeloma (MM) is unknown so far. Aims: The aim is to analyze the expression level of plasma circulating GAS5 in patients with MM at presentation and in the relapse of the disease, also to investigate its association with clinical characteristics, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Methods: This is a prospective research which includes patients with MM who were diagnosed and treated in Clinical-hospital center (CHC) Bezanijska kosa and CHC Zemun from November 2021 to October 2024. Plasma samples were collected from 72 MM patients at diagnosis and also from 6 patients at relapse. Relative quantification analysis of GAS5 expression level was performed by RQ-PCR methodology with GAPDH gene as endogenous control and using comparative ddCt method with healthy controls as calibrator. Results: This group included 38 (52.7%) males and 34 (47.3%) females; median age was 69 years (range 44-90). ISS score 1, 2 and 3 was present in 11 (15%), 17 (24%) and 44 (61%) patients; respectively. High-risk cytogenetic aberrations were present in 24 (34%) patients. Favorable therapeutic response was registered in 61 (84.7%) patients. Mortality rate was 29.1% (21 patients). Median expression of GAS5 in de novo MM patients was 0.810 (range 0.012-6.516), which was not significantly lower in comparison to expression level among healthy controls (median 1.001, range 0.660-2.435) (p=0.069). No difference was shown in expression levels of GAS5 in relapse compared to the level detected at presentation (median 0.580, range 0.021-1.830) (p=0.818). We used ROC curve analysis to determine cut-off value for the GAS5 expression and the most predictive value was 1.068 (AUC=0.6, Sensitivity=72.1%, Specificity=63.6%, p=0.034). Using this value, patients were divided into low and high GAS5 expression group (GAS5low and GAS5high). In our cohort of patients, 67% (48/72) were in GAS5low group. No correlation was found between the level of GAS5 expression and clinical characteristics. Also, the level of GAS5 expression was not associated with any cytogenetic risk group, while gain of 1q21 was more frequent in GAS5highpatients (p=0.05). Patients in GAS5low group had significantly better ORR compared to GAS5high patients (p=0.021). Moreover, survival analysis showed that GAS5lowpatients had longer OS (16.6 vs. 9 months) (Long-Rank 4.317, p=0.038), while no significant difference was shown in PFS between GAS5lowand GAS5high patients (Log-Rank 3.122, p=0.077). Summary/Conclusion: Our study showed that the level of plasma circulating GAS5 was reduced in de novo patients compared to healthy controls, but with no statistical difference. Our results imply that low GAS5 expression level could predict better ORR and OS in patients with MM.30th Congress of the European Hematology Association EHA2024 Annual Congress Edition June 202