TY - JOUR
T1 - Systematic discrimination of the repetitive genome in proximity of ferroptosis genes and a novel prognostic signature correlating with the oncogenic lncRNA CRNDE in multiple myeloma
AU - Qin, Jiading
AU - Sharma, Amit
AU - Wang, Yulu
AU - Tobar-Tosse, Fabian
AU - Dakal, Tikam Chand
AU - Liu, Hongde
AU - Liu, Hongjia
AU - Ke, Bo
AU - Kong, Chunfang
AU - Liu, Tingting
AU - Zhao, Chunxia
AU - Schmidt-Wolf, Ingo G.H.
AU - Jin, Chenghao
N1 - Publisher Copyright:
Copyright © 2022 Qin, Sharma, Wang, Tobar-Tosse, Dakal, Liu, Liu, Ke, Kong, Liu, Zhao, Schmidt-Wolf and Jin.
PY - 2022/12/20
Y1 - 2022/12/20
N2 - Emerging insights into iron-dependent form of regulated cell death ferroptosis in cancer have opened a perspective for its use in cancer therapy. Of interest, a systematic profiling of ferroptosis gene signatures as prognostic factors has gained special attention in several cancers. Herein, we sought to investigate the presence of repetitive genomes in the vicinity of ferroptosis genes that may influence their expression and to establish a prognostic gene signature associated with multiple myeloma (MM). Our analysis showed that genes associated with ferroptosis were enriched with the repetitive genome in their vicinity, with a strong predominance of the SINE family, followed by LINE, of which the most significant discriminant values were SINE/Alu and LINE/L1, respectively. In addition, we examined in detail the performance of these genes as a cancer risk prediction model and specified fourteen ferroptosis-related gene signatures, which identified MM high-risk patients with lower immune/stromal scores with higher tumor purity in their immune microenvironment. Of interest, we also found that lncRNA CRNDE correlated with a risk score and was highly associated with the majority of genes comprising the signature. Taken together, we propose to investigate the molecular impact of the repetitive genome we have highlighted on the local transcriptome of ferroptosis genes in cancer. Furthermore, we revealed a genomic signature/biomarker related to ferroptosis that can be used to predict the risk of survival in MM patients.
AB - Emerging insights into iron-dependent form of regulated cell death ferroptosis in cancer have opened a perspective for its use in cancer therapy. Of interest, a systematic profiling of ferroptosis gene signatures as prognostic factors has gained special attention in several cancers. Herein, we sought to investigate the presence of repetitive genomes in the vicinity of ferroptosis genes that may influence their expression and to establish a prognostic gene signature associated with multiple myeloma (MM). Our analysis showed that genes associated with ferroptosis were enriched with the repetitive genome in their vicinity, with a strong predominance of the SINE family, followed by LINE, of which the most significant discriminant values were SINE/Alu and LINE/L1, respectively. In addition, we examined in detail the performance of these genes as a cancer risk prediction model and specified fourteen ferroptosis-related gene signatures, which identified MM high-risk patients with lower immune/stromal scores with higher tumor purity in their immune microenvironment. Of interest, we also found that lncRNA CRNDE correlated with a risk score and was highly associated with the majority of genes comprising the signature. Taken together, we propose to investigate the molecular impact of the repetitive genome we have highlighted on the local transcriptome of ferroptosis genes in cancer. Furthermore, we revealed a genomic signature/biomarker related to ferroptosis that can be used to predict the risk of survival in MM patients.
KW - ferroptosis
KW - gene signature
KW - lncRNA – long noncoding RNA
KW - multiple myeloma
KW - prognosis
KW - repetitive genome
UR - http://www.scopus.com/inward/record.url?scp=85145480652&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.1026153
DO - 10.3389/fonc.2022.1026153
M3 - Article
AN - SCOPUS:85145480652
SN - 2234-943X
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1026153
ER -