Plasma expression of long non-coding RNA GAS5 and its prognostic significance in newly diagnosed multiple myeloma

Long non-coding RNAs (lncRNAs) participate in pathogenesis, progression and therapy resistance in multiple myeloma (MM). Growth Arrest-Specific 5 (GAS5) is a lncRNA with a role in proliferation, invasion and metastasis in solid tumors, but prognostic significance in MM is unknown so far. Aim: The purpose of this study was to examine the expression pattern of GAS5 lncRNA in plasma samples of MM patients and to evaluate its clinical and prognostic significance.

73 newly diagnosed patients with MM and 16 healthy volunteers were recruited from Clinical Hospital Centre (CHC) "Bežanijska Kosa" and CHC "Zemun" in the period from July 2020 to December 2024. Blood samples were collected before starting therapy. Demographic, laboratory and clinical parameters, prognostic score, overall response rate, progression free survival (PFS) and overall survival (OS) were analyzed. Relative quantification analysis of the GAS5 expression level was performed by RQ-PCR methodology with the GAPDH gene as endogenous control and by using the comparative ddCt method with control samples as a calibrator.

No significant difference was found between plasma expression GAS5 in MM patients (median 0.833, range 0.013-3.678) and GAS5 expression in healthy control samples (median 1, range 0.49-2.668) (p=0.116). In multivariate analysis with PFS as the dependent variable, higher GAS5 expression and advanced age were associated with shorter time to progression, while higher R2-ISS score, advanced age and occurrence of relapse/progression of disease were independent prognostic factors for survival in our group of patients.

This is the first study showing prognostic potential of circulating lncRNA GAS5 in the MM patients. Patients with MM had a slightly lower GAS5 expression compared to control samples, this was, nevertheless, without statistical significance. In patients with higher GAS5 expression disease progression occurred earlier compared to patients with lower expression. To establish GAS5 as a robust biomarker in MM, future studies should focus on larger patient cohorts to validate its expression within the bone marrow niche and its specific association with high-risk 'double-hit' cytogenetic aberrations and glucocorticoid resistance.