The prognostic potential of the long non-coding RNA MALAT1 in M0 prostate cancer


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Kenneth Hiew1,Sivan Bokobza2,Claire Hart1,Tony Elliott3,Neil Smith2,Michael Brown1,Noel Clarke3
1Genito Urinary Cancer Research Group,2AstraZeneca,3Christie Hospital NHS Foundation Trust

Abstract

Background

Prostate cancer is the most common male cancer and second most lethal cancer in men in the UK. Currently there are no biomarkers at the point of initial diagnosis which robustly identify patients who will develop metastatic disease. MALAT1 (metastasis associated lung adenocarcinoma transcript 1), a long non-coding RNA, originally identified in lung adenocarcinoma has been shown to be prognostic in lung cancer. MALAT1 has been associated with  an aggressive phenotype with increased motility in  renal and urothelial carcinomas.Its role in prostate cancer is unknown.

Method

Regions of tumour from archival FFPE TURP specimens with up to 21 years of clinical follow-up data were macro-dissected for RNA extraction.Subsequent 405 gene expression analysis used the NanoString© platform. Principle component analysis(PCA) was conducted using Qlucore Omics Explorer 3.2 with specific MALAT1 correlations analysed using  Pearson’s Coefficient Correlation. Pathway modelling was performed using DAVID Functional Annotation Clustering and statistical analysis conducted in SPSS. mRNA expression levels were assessed in cell lines of defined characteristic by qRT-PCR.

Results

PCA analysis identified a 31 gene signature, including MALAT1,  differentiating between M0 and M1 at diagnosis (p=0.0126, q=0.1044). Over expression of MALAT1 correlated with time to progression (47 months vs 120 months; p <0.05) and shorter overall survival in M0 patients at diagnosis (95 months vs 130 months; p= 0.026) but did not predict time to progression or overall survival in M1 patients. Pathway analysis suggests a link between MALAT1 and both Hedgehog and PIK3CA/Akt signalling pathways.

Conclusion

MALAT1 expression in diagnostic biopsies has prognostic potential in prostate cancer patients presenting with M0 disease.