The expression levels of long non‐coding RNA KIAA0125 are associated with distinct clinical and biological features in myelodysplastic syndromes

Abstract

Summary Long non‐coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS‐R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia‐free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS‐R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used.

Attenuated cell cycle and DNA damage response transcriptome signatures and overrepresented cell adhesion processes imply accelerated progression in patients with lower‐risk myelodysplastic neoplasms

“…The expression of lncRNAs was heterogeneous in stMDS throughout the patients, but we observed a greater uniformity and mainly upregulation in lncRNA expression in prMDS (Figure S11). In accordance with previously described lncRNAs with prognostic significance in MDS, [22][23][24] we observed upregulation of MEG3 and KIAA0125 and downregulation of TCL6 in prMDS. Multiple other lncRNAs upregulated in prMDS compared to stMDS have a known function in cancer (Table S4B).…”

“…most significantly upregulated lncRNA in prMDS was KIAA0125; its higher expression has previously been associated with concordant upregulation of HSC-associated genes at higher-risk MDS and has emerged as an independent unfavorable prognostic marker for OS and LFS in MDS. 22 Indeed, lncRNAs belong to important epigenetic regulators of tumor-promoting and tumor-restraining pathways and contribute to the regulation of expression of multiple oncogenes and tumor-suppressor genes. 47 Because epigenetic silencing of DDR genes and pathways is a common cause of DDR deficiency in cancer, 38 we correlated two of the significantly overexpressed oncogenic lncRNAs in prMDS, LINC00340 (CASC15) and MALAT1, with their potentially interacting components of DDR pathway (ZEB1 and CDKN1A in the case of LINC00340, and PARP1…”

A CIBERSORTx-based immune cell scoring system could independently predict the prognosis of patients with myelodysplastic syndromes

“…Our bioinformatic analyses revealed the significant correlation between high immune cell risk scores and LSC signatures, NF-κB signaling, and oxidative stress characteristics. Recent studies have shown that LSC signatures are associated with higher risk of disease progression and mortality in MDS patients and can serve as prognostic markers independent of R-IPSS risk and genomic alterations 48,49 . Constitutive activation of NF-κB signaling has been known to play a critical role in MDS pathophysiology and as a feature of high-risk MDS 7,8,[50][51][52][53][54] .…”

Hypoplastic myelodysplastic syndrome and acquired aplastic anemia: Immune‑mediated bone marrow failure syndromes (Review)

“…In relation to the skewed T cell repertoire in MDS, pathway analysis of differentially expressed genes between patients with the highest and lowest lncRNA risk scores determined T cell-related pathways [e.g., cytotoxic T-lymphocyte-associated protein 4 signaling in cytotoxic T lymphocytes and CD28 signaling in T helper (Th) cells] to be the most significant (60). Hung et al (63) recently identified an association between higher KIAA0125 expression (BM mononuclear cells) and high-risk MDS, ASXL1 and NRAS mutations, and poorer OS and leukemia-free survival. A recent study by Li et al (64) reported an association between a higher expression level of LOC101928834 and a higher white blood cell count, a higher blast percentage, RAEB subtype and a shorter OS time in MDS.…”