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Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.

ABSTRACT: Hypoxia promotes tumour aggressiveness and reduces patient survival. A spectrum of poor outcome among patients with hypoxic tumours suggests that additional factors modulate how tumours respond to hypoxia. PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with a pivotal role in genomic stability and epigenetic regulation of gene expression. We reported that cancer type-specific piRNA signatures vary among patients. However, remarkably homogenous piRNA profiles are detected across patients with renal cell carcinoma, a cancer characterized by constitutive upregulation of hypoxia-related signaling induced by common mutation or loss of von Hippel-Lindau factor (VHL). By investigating >3000 piRNA transcriptomes in hypoxic and non-hypoxic tumors from seven organs, we discovered 40 hypoxia-regulated piRNAs and validated this in cells cultured under hypoxia. Moreover, a subset of these hypoxia-regulated piRNAs are regulated by VHL/HIF signaling in vitro. A hypoxia-regulated piRNA-based score (PiSco) was associated with poor RFS for hypoxic tumours, particularly Stage I lung adenocarcinomas, suggesting that hypoxia-regulated piRNA expression can predict tumour recurrence even in early-stage tumours and thus may be of clinical utility.

SUBMITTER: Martinez VD

PROVIDER: S-EPMC5760628 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.

Martinez Victor D VD Firmino Natalie S NS Marshall Erin A EA Ng Kevin W KW Wadsworth Brennan J BJ Anderson Christine C Lam Wan L WL Bennewith Kevin L KL

Scientific reports 20180109 1

Hypoxia promotes tumour aggressiveness and reduces patient survival. A spectrum of poor outcome among patients with hypoxic tumours suggests that additional factors modulate how tumours respond to hypoxia. PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with a pivotal role in genomic stability and epigenetic regulation of gene expression. We reported that cancer type-specific piRNA signatures vary among patients. However, remarkably homogenous piRNA profiles are detected across patients ...[more]

PMID: 29317756

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Project description:BackgroundBladder cancer (BC) is regarded as one of the most fatal cancer around the world. Nevertheless, there still lack of sufficient markers to predict the prognosis of BC patients. Herein, we aim to establish a prognosis predicting signature based on long-noncoding RNA (lncRNA) for the invasive BC patients.MethodsThe lncRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, along with the correlated clinicopathological information. The univariate Cox regression test was employed to screen out the recurrence-free survival (RFS)-related lncRNAs. Then, the LASSO method was conducted to construct the signature based on these RFS-related lncRNA candidates. Genes correlated with these fourteen lncRNAs were extracted from the mRNA expression profile, with the Pearson correlation coefficient?>?0.60 or?<?-?0.40. Subsequently, the Proteomap pathway enrichment analyses were conducted to classify the function of these correlated genes. Furthermore, the multivariate analyses were executed to reveal the independent role of the proposed signature with the clinicopathological features.ResultsWe established an lncRNA-based RFS predicting signature by the LASSO Cox regression test, and proved its usage and stability on both the training and validation cohorts by the Kaplan-Meier and receiver operating characteristic (ROC) curves. Notably, the multivariate Cox regression analysis found that our classifier was an independent indicator for muscle-invasive BC patients rather than sex, age and tumor grade, with higher predictive value than the existing ones. Besides, we did the pathway analyses for these genes that highly correlated with the proposed fourteen lncRNAs, as well as the differentially expressed genes (DEGs) derived from the high-risk vs. low-risk groups, and the recurrence vs. non-recurrence groups, respectively. Notably, these results were consistent, and these genes were mostly enriched in the transcription factors, G protein-coupled receptors, MAPK signaling pathways, which were proved significantly associated with tumor progression and drug resistance.ConclusionsOur results suggested that the fourteen-lncRNA-based RFS predicting signature is an independent indicator for BC patients. Further prospective studies with more samples are needed to verify our findings.

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Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.

Publications

Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.

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