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Molecular Classification of Breast Cancer Utilizing Long Non-Coding RNA (lncRNA) Transcriptomes Identifies Novel Diagnostic lncRNA Panel for Triple-Negative Breast Cancer.

ABSTRACT: Breast cancer remains the world's most prevalent cancer, responsible for around 685,000 deaths globally despite international research efforts and advances in clinical management. While estrogen receptor positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor positive (HER2+) subtypes are easily classified and can be targeted, there remains no direct diagnostic test for triple-negative breast cancer (TNBC), except for the lack of receptors expression. The identification of long non-coding RNAs (lncRNAs) and the roles they play in cancer progression has recently proven to be beneficial. In the current study, we utilize RNA sequencing data to identify lncRNA-based biomarkers associated with TNBC, ER+ subtypes, and normal breast tissue. The Marker Finder algorithm identified the lncRNA transcript panel most associated with each molecular subtype and the receiver operating characteristic (ROC) analysis was used to validate the diagnostic potential (area under the curve (AUC) of ≥8.0 and p value < 0.0001). Focusing on TNBC, findings from the discovery cohort were validated in an additional two cohorts, identifying 13 common lncRNA transcripts enriched in TNBC. Binary regression analysis identified a four lncRNA transcript signature (ENST00000425820.1, ENST00000448208.5, ENST00000521666.1, and ENST00000650510.1) with the highest diagnostic power for TNBC. The ENST00000671612.1 lncRNA transcript correlated with worse refractory free survival (RFS). Our data provides a step towards finding a novel diagnostic lncRNA-based panel for TNBC with potential therapeutic implications.

SUBMITTER: Shaath H

PROVIDER: S-EPMC8582428 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBreast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients.MethodsSystematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores.ResultsOur study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model.ConclusionOur study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.

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Molecular Classification of Breast Cancer Utilizing Long Non-Coding RNA (lncRNA) Transcriptomes Identifies Novel Diagnostic lncRNA Panel for Triple-Negative Breast Cancer.

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