A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells

Lili Zhu; Kang Cui; Lanling Weng; Pu Yu; Yabing Du; Tengfei Zhang; Hong Liu; Bingjie Li; Wang Ma

doi:10.1371/journal.pone.0249174

A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells

PLoS One. 2021 Jun 4;16(6):e0249174. doi: 10.1371/journal.pone.0249174. eCollection 2021.

Authors

Lili Zhu^{1

2}, Kang Cui¹, Lanling Weng^{1

2}, Pu Yu¹, Yabing Du¹, Tengfei Zhang¹, Hong Liu¹, Bingjie Li¹, Wang Ma¹

Affiliations

¹ Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Academy of Medical Science, Zhengzhou University, Zhengzhou, China.

Abstract

Background: Breast 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.

Methods: Systematic 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.

Results: Our 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.

Conclusion: Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor / genetics
Breast Neoplasms / genetics*
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Movement / genetics*
Female
Gene Expression Profiling / methods
Gene Expression Regulation, Neoplastic / genetics
Humans
Kaplan-Meier Estimate
MCF-7 Cells
Prognosis
RNA, Long Noncoding / genetics*
Signal Transduction / genetics

Substances

Biomarkers, Tumor
RNA, Long Noncoding

Grants and funding

This work was supported by the National Natural Science Foundation of China (31570917), and the Doctoral team foundation of the First Affiliated Hospital of Zhengzhou University. The owner of the fundings is MW. He joined the study design.