In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5719-5719
Abstract:
RNA has diverse sets of regulatory functions and a recent analysis of RNA repertoire has identified a large numbers of non-coding transcripts. One of which, long intergenic non-coding RNA (lincRNA) with transcripts longer than 200 nucleotides, are located between the protein coding genes and do not overlap exons of either protein-coding or other non-lincRNA genes. lincRNAs have been considered to provide regulatory functions, however, their precise role in cellular biology remains unclear. Here, we have studied lincRNAs using uniformly treated patients to show their impact on survival outcome in MM. We performed RNA-seq on CD138+ MM cells from 360 newly-diagnosed patients and 18 normal plasma cells (NPM) and analyzed for lincRNA and protein coding genes. MM patient data for clinical characteristics, cytogenetic and FISH as well as clinical survival outcomes were also analyzed and correlated with lincRNA data. Our data showed expression of 951 lincRNAs (median TPM & gt; 1) with 351 lincRNAs differentially expressed between MM and normal plasma cells. Using only the expressed lincRNAs, we applied log rank tests for quartile 1 (Q1) versus Q2 through Q4 and Q4 versus Q1 through Q3 in order to identify under- and overexpressed prognostic genes, respectively. Four under and seven overexpressed genes were selected for final model. We used Más-o-menos for final predictive model, which simply calculates the risk score, by using expression values. The Kaplan-Meier estimates of EFS at 4 years were 53.3% (95% CI, 45.1% to 63.1%) and 32.6% (95% CI, 25.1% to 42.2%), and OS at 4 years were 93.2% (95% CI, 88.9% to 97.6%) and 71.1% (95% CI, 62.9% to 80.3%) in our patients having a low or high risk score. When applied to patient cohort separated by other risk categorization including minimal residual disease status (MRD), cytogenetic risk status (del17p, t(4;14) and t(14;16)) and International Staging System (ISS), lincRNA signature was able to further identify patients with significant differential survival outcomes. In summary, we report that lincRNAs have an independent effect on survival outcome in MM and provides rational for its use in risk stratification as well as to understand biological impact. Citation Format: Mehmet K. Samur, Annamaria Gulla, Mariateresa Fulciniti, Anil Aktas Samur, Raphael Szalat, Masood Shamas, Florence Magrangeas, Stephane Minvielle, Kenneth Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Nikhil Munshi. Long intergenic non-coding RNAs: a new independent risk predictors in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5719. doi:10.1158/1538-7445.AM2017-5719
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-5719
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
