Dataset Information

Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach.

ABSTRACT: Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and long non-coding(lnc)-SAYSD1-1, able to discriminate ERG/not-ERG subtypes, were demonstrated to be positive prognostic biomarkers in ERG-positive patients. Furthermore, we performed a comparison between mutated prostate cancer, identified as "classified", and a group of patients with no peculiar genomic alteration, named "not-classified". Moreover, LINC00920 lncRNA overexpression has been linked to a better outcome of the hormone regimen. Through the feature selection approach, it was found that the overexpression of lnc-ZMAT3-3 is related to low-grade patients, and three lncRNAs: lnc-SNX10-87, lnc-AP1S2-2, and ADPGK-AS1 showed, through a co-expression analysis, significant correlation values with potentially druggable pathways. In conclusion, the data mining of publicly available data and robust bioinformatic analyses are able to explore the unknown biology of malignancies.

SUBMITTER: De Summa S

PROVIDER: S-EPMC7926489 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach.

De Summa Simona S Palazzo Antonio A Caputo Mariapia M Iacobazzi Rosa Maria RM Pilato Brunella B Porcelli Letizia L Tommasi Stefania S Paradiso Angelo Virgilio AV Azzariti Amalia A

International journal of molecular sciences 20210223 4

Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and lon ...[more]

PMID: 33672425

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Project description:BackgroundThe unveiling of long non-coding RNAs as important gene regulators in many biological contexts has increased the demand for efficient and robust computational methods to identify novel long non-coding RNAs from transcripts assembled with high throughput RNA-seq data. Several classes of sequence-based features have been proposed to distinguish between coding and non-coding transcripts. Among them, open reading frame, conservation scores, nucleotide arrangements, and RNA secondary structure have been used with success in literature to recognize intergenic long non-coding RNAs, a particular subclass of non-coding RNAs.ResultsIn this paper we perform a systematic assessment of a wide collection of features extracted from sequence data. We use most of the features proposed in the literature, and we include, as a novel set of features, the occurrence of repeats contained in transposable elements. The aim is to detect signatures (groups of features) able to distinguish long non-coding transcripts from other classes, both protein-coding and non-coding. We evaluate different feature selection algorithms, test for signature stability, and evaluate the prediction ability of a signature with a machine learning algorithm. The study reveals different signatures in human, mouse, and zebrafish, highlighting that some features are shared among species, while others tend to be species-specific. Compared to coding potential tools and similar supervised approaches, including novel signatures, such as those identified here, in a machine learning algorithm improves the prediction performance, in terms of area under precision and recall curve, by 1 to 24%, depending on the species and on the signature.ConclusionsUnderstanding which features are best suited for the prediction of long non-coding RNAs allows for the development of more effective automatic annotation pipelines especially relevant for poorly annotated genomes, such as zebrafish. We provide a web tool that recognizes novel long non-coding RNAs with the obtained signatures from fasta and gtf formats. The tool is available at the following url: http://www.bioinformatics-sannio.org/software/ .

Project description:BackgroundEnhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic.MethodsFirstly, STAD were clustered into three subtypes with the data of eRNA expression from TCeA. Then we explored the difference of the tumor immune microenvironment, transcription levels, and transcription regulation among the three clusters. Finally, samples collected from 12 patients diagnosed with STAD were used to conduct qRT-PCR, verifying the conclusion based on network database.ResultsThe three clusters were detected to have different tumor microenvironments: Cluster A has an immune "cold" microenvironment. While cluster B features as more infiltration of immune cells, accompanied with higher expression of immune checkpoints such as PDCD1, LAG3, and TIGIT. Besides, Cluster C shows a higher stromal feature with B lineage, neutrophils, and fibroblasts. Further analyses indicated that CpG island methylation level of Cluster B is different from the other two clusters. Meanwhile, Cluster A and B showed significant enrichment of TP53 and KRAS mutation respectively while Cluster C has higher tumor mutation burden (TMB) and microsatellite instability (MSI). With the elaboration of transcriptional regulation of epigenetic clustering, we detected that Cluster A enriched in epithelial phenotype pathways. Cluster B enriched in cell-cell adhesion. Cluster C enriched in fibroblast proliferation. The clinical cohort show that Cluster B patients have lower interstitial cell characteristics and CAF infiltration.ConclusionWe identified three unique epigenetic clusters of STAD through the differential activation of super-enhancers, and identified Cluster B with a higher immune infiltrating and a better prognosis, which provides a novel understanding of eRNAs and potential clinical applicability of eRNA-based molecular subtypes in gastric cancer.

Dataset Information

Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach.

Publications

Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach.

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