Multiple myeloma is a hematological cancer of plasma B-cells and remains incurable. Two major subtypes of myeloma, hyperdiploid (HMM) and non-hyperdiploid myeloma (NHMM), have distinct chromosomal alterations and differential survival outcomes. Transcription factors (TFs) such as NF-κB and MYC are over-activated in some myeloma patients and implicated in oncogenesis. Dysregulation of cyclins are also proposed as a unifying event in myeloma. Here we have developed a TF-pathway co-expression analysis to identify TFs that have significant co-expression changes with the cell cycle arrest pathway between two myeloma subtypes. We have found that MYC, NF-κB and HOXA9 genes have significantly lower co-expression with the cell cycle arrest pathway in HMM, co-occurring with their over-activation in HMM. In contrast, ESR1, SP1 and E2F1 have significantly lower co-expression with the cell cycle arrest pathway in NHMM. We propose a cooperation model of ESR1 and SP1 in regulating cell cycle arrest. Drug combination treatment of four NHMM cell lines shows that co-targeting ESR1 and SP1 has synergistic effect on inhibiting myeloma proliferation. We provide the TF-PathCo analysis method for use in other cancers and diseases: here
co-expression analysis require Hotelling R package. The codes contain co-expression analysis, Bayesian meta analysis and Permutation.
Developed by Cheng Li Lab.