RGD Reference Report - Development of an RNA sequencing-based prognostic gene signature in multiple myeloma. - Rat Genome Database

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Development of an RNA sequencing-based prognostic gene signature in multiple myeloma.

Authors: Zamani-Ahmadmahmudi, Mohamad  Nassiri, Seyed Mahdi  Soltaninezhad, Fatemeh 
Citation: Zamani-Ahmadmahmudi M, etal., Br J Haematol. 2021 Jan;192(2):310-321. doi: 10.1111/bjh.16744. Epub 2020 May 15.
RGD ID: 155900765
Pubmed: PMID:32410217   (View Abstract at PubMed)
DOI: DOI:10.1111/bjh.16744   (Journal Full-text)

Several prognostic gene signatures have been developed to predict the clinical outcome in patients with multiple myeloma (MM). The most salient disadvantage of the previous signatures is their non-reproducibility in external datasets. Given the disadvantages and the superiority of RNA sequencing over microarrays in transcriptome profiling to produce more reliable outputs, we sought to develop a reproducible RNA sequencing-based prognostic gene signature for MM. Genes significantly associated with survival were detected in The Cancer Genome Atlas (TCGA) MM RNA sequencing dataset (MMRF-CoMMpass) (n = 412) through a strict pipeline containing four rigid filters. The reproducibility of the selected genes was checked in an independent dataset (GSE24080), containing 559 newly diagnosed patients with MM. The RNA sequencing-based prognostic signature was reconstructed based on the final genes in the training dataset (MMRF-CoMMpass) and externally validated in five independent datasets (i.e. GSE2658, GSE13624, GSE9782, GSE6477 and GSE57317), containing 1461 MM cases. The RNA sequencing-based signature was reconstructed using finally five reproducible genes: CCT2, CKS1B, PRKDC, NONO and UBE2A. This signature was able to robustly discriminate between low- and high-risk patients in both training and validation datasets (Ps <= 0·001). Our signature was also independent of and more powerful than the routine MM prognostic factors (i.e. β2-microglobulin, albumin, age and sex) (Ps <= 0·01). Treatment regimens had no effect on RNA sequencing-based signature insofar as this signature succeeded in predicting the clinical outcome in various treatment groups (Ps <= 0·001).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
multiple myeloma exacerbatesIEP 155900765mRNA:increased expression: (human)RGD 
multiple myeloma exacerbatesISONONO (Homo sapiens)155900765; 155900765mRNA:increased expression: (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nono  (non-POU domain containing, octamer-binding)

Genes (Mus musculus)
Nono  (non-POU-domain-containing, octamer binding protein)

Genes (Homo sapiens)
NONO  (non-POU domain containing octamer binding)


Additional Information