Loss of GAS5 tumour suppressor lncRNA: an independent molecular cancer biomarker for short-term relapse and progression in bladder cancer patients

Abstract

BackgroundBladder cancer (BlCa) heterogeneity and the lack of personalised prognosis lead to patients’ highly variable treatment outcomes. Here, we have analysed the utility of the GAS5 tumour-suppressor lncRNA in improving BlCa prognosis.MethodsGAS5 was quantified in a screening cohort of 176 patients. Hedegaard et al. (2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts. Survival analysis was performed using recurrence and progression for NMIBC, or death for MIBC. Internal validation was performed by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit on disease prognosis.ResultsGAS5 levels were significantly downregulated in BlCa and associated with invasive high-grade tumours, and high EORTC-risk NMIBC patients. GAS5 loss was strongly and independently correlated with higher risk for NMIBC early relapse (HR = 2.680, p = 0.011) and progression (HR = 6.362, p = 0.035). Hedegaard et al. and TCGA validation cohorts’ analysis clearly confirmed the association of GAS5 loss with NMIBC worse prognosis. Finally, multivariate models incorporating GAS5 with disease established markers resulted in higher clinical benefit for NMIBC prognosis.ConclusionsGAS5 loss is associated with adverse outcome of NMIBC and results in improved positive prediction of NMIBC patients at higher risk for short-term relapse and progression, supporting personalised prognosis and treatment decisions.

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

“…91 GAS5 expression was commonly downregulated in BCa specimens and cells. [92][93][94][95] For example, lower levels of GAS5 were found in 82 bladder transitional cell carcinomas (BTCC) tissues and cells and were correlated with high pathological grades and short DFS time for BTCC patients. 94 Low GAS5 levels was also associated with invasive high-grade tumors, and high European Organization for Research and Treatment of Cancer (EORTC) risk in non-muscle-invasive bladder cancer (NMIBC) patients, and GAS5 loss was correlated with a higher risk for NMIBC short-term relapse and progression, making GAS5 a prognosis biomarker for NMIBC patients.…”

“…94 Low GAS5 levels was also associated with invasive high-grade tumors, and high European Organization for Research and Treatment of Cancer (EORTC) risk in non-muscle-invasive bladder cancer (NMIBC) patients, and GAS5 loss was correlated with a higher risk for NMIBC short-term relapse and progression, making GAS5 a prognosis biomarker for NMIBC patients. 95 Together, acting as a tumor suppressor, GAS5 provided a novel therapeutic strategy and a potential diagnostic and prognostic biomarker for BCa. Glioma is a type of neurologically destructive human brain tumors with a poor prognosis, which accounts for nearly 80% of malignant brain tumors and 30% of all central nervous system tumors.…”

A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma

“…Accumulating evidence indicates that lncRNAs participate in many physiological and pathological processes [22,23]. In this study, we investigated lncRNA expression profiles in response to IFNα stimulation in HNSCC cells and identified a novel IFNα-induced lncRNA, lncMX1-215.…”

Bioinformatics analysis of prognosis-related long non-coding RNAs in invasive breast carcinoma

“…Long non-coding RNAs (lncRNAs) are non-coding transcripts, usually >200 nucleotides in length (3). Increasing evidence suggests that lncRNAs are important regulators in multiple biological processes and that lncRNAs with aberrant expression levels are involved in cancer development and may be potential diagnostic biomarkers for cancer (3)(4)(5). MicroRNAs (miRNAs) are a class of small non-coding RNAs which serve an important role in the gene regulation network (6).…”