Identification of Genomic Instability-Associated LncRNAs as Potential Therapeutic Targets in Lung Adenocarcinoma
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
identifier citation: Cancers 17 (6): 996 (2025)
contributor: BC Cancer Research Centre
contributor: University of British Columbia. Interdisciplinary Oncology Program
creator: Souza, Vanessa G. P.
creator: Benard, Katya H.
creator: Stewart, Greg L.
creator: Enfield, Katey S. S.
creator: Lam, Wan
issued: 2025-05-09T14:00:18Z
issued: 2025-03-15
description: Background/Objectives: Non-small cell lung cancer (NSCLC) is the most common type of cancer, with lung adenocarcinoma (LUAD) as the predominant subtype. Despite advancements in targeted therapies, many NSCLC patients still experience poor outcomes due to treatment resistance and disease progression. Genomic instability (GI), a hallmark of cancer, defined as the increased tendency of DNA mutations and alterations, is closely linked to cancer initiation, progression, and resistance to therapy. Emerging evidence suggests that long non-coding RNAs (lncRNAs)—molecules longer than 200 nucleotides that do not encode proteins but regulate gene expression—play critical roles in cancer biology and are associated with GI. However, the relationship between GI and lncRNA expression in LUAD remains poorly understood. Methods: In this study, we analyzed the transcript profiles of lncRNAs and mRNAs from LUAD samples in The Cancer Genome Atlas (TCGA) database and classified them based on their Homologous Recombination Deficiency (HRD) score. The HRD score is an unweighted sum of three independent DNA-based measures of genomic instability: loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions. We then performed a differential gene expression analysis to identify lncRNAs and mRNAs that were either upregulated or downregulated in samples with high HRD scores compared to those with low HRD scores. Following this, we conducted a correlation analysis to assess the significance of the association between HRD scores and the expression of both lncRNAs and mRNAs. Results: We identified 30 differentially expressed lncRNAs and 200 mRNAs associated with genomic instability. Using an RNA interactome database from sequencing experiments, we found evidence of interactions between GI-associated lncRNAs (GI-lncRNAs) and GI-associated mRNAs (GI-mRNAs). Further investigation showed that some GI-lncRNAs play regulatory and functional roles in LUAD and other diseases. We also f…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/91073
note: Academic Editor: Akiteru GotoReceived: 12 February 2025Revised: 11 March 2025Accepted: 13 March 2025Published: 15 March 2025Citation: Souza, V.G.P.; Benard, K.H.;Stewart, G.L.; Enfield, K.S.S.; Lam,W.L. Identification of GenomicInstability-Associated LncRNAs asPotential Therapeutic Targets in LungAdenocarcinoma. Cancers 2025, 17, 996.https://doi.org/10.3390/cancers17060996Copyright: © 2025 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license(https://creativecommons.org/licenses/by/4.0/).ArticleIdentification of Genomic Instability-Associated LncRNAs asPotential Therapeutic Targets in Lung AdenocarcinomaVanessa G. P. Souza 1,*,† , Katya H. Benard 1,2,†, Greg L. Stewart 1,2, Katey S. S. Enfield 1,2,3 and Wan L. Lam 1,2,31 British Columbia Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada; wanlam@bccrc.ca (W.L.L.)2 Interdisciplinary Oncology Program, University of British Columbia, Vancouver, BC V6T 1Z4, Canada3 Department of Pathology and Laboratory Medicine, University of British Columbia,Vancouver, BC V6T 1Z7, Canada* Correspondence: vsouza@bccrc.ca† These authors contributed equally to this work.Simple Summary: Non-small cell lung cancer (NSCLC) is the most common type of lungcancer, with lung adenocarcinoma (LUAD) being its predominant subtype. Despite ad-vancements in treatment, LUAD outcomes remain poor due to treatment resistance, whichis in part driven by genomic instability (GI)—an increased tendency for DNA mutationsand other genetic changes that occur during cell division. Using LUAD samples fromThe Cancer Genome Atlas (TCGA) database, we classified cases by Homologous Recom-bination Deficiency (HRD) score—a measure of GI—and identified 30 long non-codingRNAs (lncRNAs) and 200 messenger RNAs (mRNAs) associated with GI. We found thatGI-associated lncRNAs (GI-lncRNAs) could serve as prognostic biomarkers, particularlywhen combi…
has type: Article
is shown at: 10.14288/1.0448825
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/cancers17060996
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: genomic instability
subject: homologous recombination deficiency (HRD)
subject: long non-coding RNAs (lncRNAs)
subject: non-small cell lung cancer (NSCLC)
type: Text
identifier URI: http://hdl.handle.net/2429/91073