Next Article in Journal
Single-Cell NGS-Based Analysis of Copy Number Alterations Reveals New Insights in Circulating Tumor Cells Persistence in Early-Stage Breast Cancer
Next Article in Special Issue
Cancer of Unknown Primary: Challenges and Progress in Clinical Management
Previous Article in Journal
Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors
Previous Article in Special Issue
lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System
Article

lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

1
IRCCS SDN, Via E. Gianturco 113, 80143 Napoli, Italy
2
Department of Paediatric Hematology–Oncology, Santobono-Pausilipon Hospital, 80143 Naples, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(9), 2489; https://doi.org/10.3390/cancers12092489
Received: 24 July 2020 / Revised: 24 August 2020 / Accepted: 31 August 2020 / Published: 2 September 2020
Acute lymphoblastic leukemia (ALL) is one of the most common childhood cancers. The ALL onset involves abnormal proliferation and arrest of differentiation of B or T cell progenitors. Recently, long non–coding RNAs (lncRNAs) gained great interest in the B–ALL leukemogenesis, however, so far few “omic” studies investigate lncRNAs and protein–coding gene networks. In our retrospective study, we conceived an integrated bioinformatic approach, by using NGS platform, to discover lncRNAs strongly correlated with aberrantly expressed protein–coding genes. We provided dysregulated lncRNA–mRNA pairs potentially underlying B–ALL pathogenesis. Diagnosis incidence peak of ALL appears approximatively between 1 and 19 years old. lncRNAs may be of clinical utility as non–invasive biomarker for B–ALL onset or therapy response in support of precision medicine. The identification of lncRNA as key regulators in B–ALL could lead to the identification of the altered pathways able to sustain the leukemic growth.
Long non–coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B–ALL). In this pilot study, we used RNA–Seq transcriptomic data for identifying novel lncRNA–mRNA cooperative pairs involved in childhood B–ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B–ALL lncRNA signatures. We then constructed a co–expression network of the aberrantly expressed lncRNAs (30) and protein–coding genes (754). We cross–validated our in–silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co–expressed mRNAs through ex vivo experiments. Using the guilt–by–association approach, we predicted lncRNA functions based on their perfectly co–expressed mRNAs (Spearman’s correlation) that resulted closely disease–associated. We shed light on 24 key lncRNAs and their co–expressed mRNAs which may play an important role in B–ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B–ALL management. View Full-Text
Keywords: RNA–Sequencing; long non–coding RNA; leukaemia; diagnostic; bioinformatics; biomarker; NGS; network; co–expression; feature extraction RNA–Sequencing; long non–coding RNA; leukaemia; diagnostic; bioinformatics; biomarker; NGS; network; co–expression; feature extraction
Show Figures

Figure 1

MDPI and ACS Style

Affinito, O.; Pane, K.; Smaldone, G.; Orlandella, F.M.; Mirabelli, P.; Beneduce, G.; Parasole, R.; Ripaldi, M.; Salvatore, M.; Franzese, M. lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study. Cancers 2020, 12, 2489. https://doi.org/10.3390/cancers12092489

AMA Style

Affinito O, Pane K, Smaldone G, Orlandella FM, Mirabelli P, Beneduce G, Parasole R, Ripaldi M, Salvatore M, Franzese M. lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study. Cancers. 2020; 12(9):2489. https://doi.org/10.3390/cancers12092489

Chicago/Turabian Style

Affinito, Ornella, Katia Pane, Giovanni Smaldone, Francesca M. Orlandella, Peppino Mirabelli, Giuliana Beneduce, Rosanna Parasole, Mimmo Ripaldi, Marco Salvatore, and Monica Franzese. 2020. "lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study" Cancers 12, no. 9: 2489. https://doi.org/10.3390/cancers12092489

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop