Autophagy-related genes affect the survival of multiple myeloma patients depending on chromosomal abnormality.

Abstract

Background: Targeting autophagy at gene level may be promising in multiple myeloma (MM) treatment depending on chromosomal abnormality (ABN) status.

Objectives: We aimed to investigate the role of ABN on survival of MM patients and to identify prognosis related autophagy-related genes (ARGs) for patients with or without ABN.

Methods: Gene intensity values of 222 ARG for 548 MM patients were obtained from the Affymetrix Human Genome U133 Plus 2.0 Array (GPL570) platform containing 54,675 probes (GSE24080). A dataset containing data from 1576 MM patients with 1q21 amplification (GSE4204, GSE4452, GSE4581, and GSE2658) was used for validation. Survival analysis of the patients was analyzed using univariate and multivariate Cox regression method with the help of R3.53 programming language and Kaplan-Meier graphics were created. The Gene Ontology enRIchmentanaLysis and visuaLizAtion (GOrilla) tool was used to define the related biological processes and pathways.

Results: The overall survival (OS) and event-free survival (EFS) in all MM patients were strongly influenced by ABN. In the group of patients with ABN, 41 ARGs were found to be important in prognosis, whereas in the group of patients without ABN, 13 ARGs were found to be important in prognosis. CDKN1A, FKBP1B, FOXO3, and NCKAP1 ARGs were commonly significant in both groups and found to be survival triggering.

Conclusions: The classification of MM patients according to the absence or presence of ABN is important in the determination of survival status. Detection of survival related ARGs in patients with chromosomal anomalies may be a new therapeutic target in treatment.