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Association between lincRNA expression and overall survival for patients with triple-negative breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication.

Methods

To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS).

Results

Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log2[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05).

Conclusions

Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Regina Courtney for her help with RNA sample preparation and Dr. Mary Shannon Byers for assistance with editing and manuscript preparation.

Funding

This study was supported by grants from the US Department of Defense (DOD) Breast Cancer Research Program (DAMD 17-02-1-0607 to X.-O. Shu) and the National Institutes of Health (NIH; R01 CA118229 to X.-O. Shu, P50CA098131 to C. Arteaga, U01CA202979 to W. J. Blot and W. Zheng). Sample preparation was conducted at the Survey and Biospecimen Shared Resources, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485).

Author information

Author notes

  1. Jie Ping and Shuya Huang have contributed equally to this work.

Authors and Affiliations

  1. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37203, USA

    Jie Ping, Shuya Huang, Jie Wu, Timothy Su, Hui Cai, Xingyi Guo, Loren Lipworth, William J. Blot, Wei Zheng, Qiuyin Cai & Xiao-Ou Shu

  2. Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, 250033, Shandong, People’s Republic of China

    Shuya Huang

  3. Department of Chronic Non-Communicable Disease Surveillance, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China

    Pingping Bao & Kai Gu

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  1. Jie Ping
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Contributions

Conceptualization: JP, SH, QC and XS. Data curation: PB, KG, JW, TS, WJB, WZ, QC and XS. Statistical analysis: JP and HC. In vitro Experiment: SH and JW. Funding acquisition: WJB, WZ and XS. Study supervision: QC and XS. Manuscript drafting: JP and SH. Critical review and final approval: All authors.

Corresponding author

Correspondence to Xiao-Ou Shu.

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None of the authors have a conflict of interest.

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The study protocol was approved by the institutional review boards of Vanderbilt University and the Shanghai Municipal Center for Disease Control and Prevention.

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All participants provided written informed consent.

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Ping, J., Huang, S., Wu, J. et al. Association between lincRNA expression and overall survival for patients with triple-negative breast cancer. Breast Cancer Res Treat 186, 769–777 (2021). https://doi.org/10.1007/s10549-020-06021-6

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