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lncRNA TCL6 correlates with immune cell infiltration and indicates worse survival in breast cancer

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Abstract

Background

Long non-coding RNA (lncRNA) T-cell leukemia/lymphoma 6 (TCL6) has been reported as a potential tumor suppressor. However, its expression and function in breast cancer remain unknown. This study was performed to investigate the expression of lncRNA TCL6 in breast cancer and its clinical significance.

Methods

The survival and clinical molecular roles of TCL6 in breast cancer were analyzed. The underlying mechanism modulated by TCL6 and its correlation with immune-infiltrating cells were investigated. Gene Expression Omnibus (GEO) datasets were further used to confirm the prognostic role of TCL6.

Results

TCL6 low expression was not correlated with age, clinical stage, T stage, lymph node metastasis, distant metastasis, human epidermal growth factor 2 status, but was associated with estrogen receptor and progesterone receptor (PR) status and was an independent factor for worse survival (HR 1.876, P = 0.016). Specifically, low TCL6 expression correlated with worse prognosis in PR-negative patients. TCL6 could predict worse survival in luminal B breast cancer based on intrinsic subtypes. Immune-related pathways such as Janus kinase–signal transducer of activators of transcription were regulated by TCL6. Further finding revealed that TCL6 correlated with immune infiltrating cells such as B cells (r = 0.25, P < 0.001), CD8+ T cells (r = 0.23, P < 0.001), CD4+ T cells (r = 0.25, P < 0.001), neutrophils (r = 0.21, P < 0.001), and dendritic cells (r = 0.27, P < 0.001). TCL6 was also positively correlated with tumor-infiltrating lymphocytes infiltration and PD-1, PD-L1, PD-L2, and CTLA-4 immune checkpoint molecules (P < 0.001).

Conclusion

Our findings suggest that lncRNA TCL6 correlates with immune infiltration and may act as a useful prognostic molecular marker in breast cancer.

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Abbreviations

TCL6:

T-cell leukemia/lymphoma 6

lncRNA:

Long non-coding RNA

HER-2:

Human epidermal growth factor 2

ER:

Estrogen receptor

PR:

Progesterone receptor

TN:

Triple negative

DC:

Dendritic cells

OS:

Overall survival

TMM:

Trimmed mean of M values

GSEA:

Gene set enrichment analysis

NES:

Normalized enrichment score

FDR:

False discovery rate

TCGA:

The Cancer Genome Atlas

GEO:

Gene Expression Omnibus

TIICs:

Tumor-infiltrating immune cells

TIL:

Tumor-infiltrating lymphocytes

TME:

Tumor microenvironment

VEGF:

Vascular endothelial growth factor

TLR:

Toll-like receptor

JAK/STAT:

Janus kinase–signal transducer of activators of transcription

PD-1:

Programmed death 1

PD-L1:

Programmed cell death 1 ligand 1

PD-L2:

Programmed cell death 1 ligand 2

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen 4

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Acknowledgements

We gratefully acknowledge The Cancer Genome Atlas and Gene Expression Omnibus.

Funding

This study was funded by the Zhejiang Medical and Health Science and Technology Plan Project (Grant number: 2015KYB432).

Author information

Author notes

  1. Yaqiong Zhang and Zhaoyun Li contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Taizhou Central Hospital Affiliated to Taizhou College, No. 999 Donghai Road, Jiaojiang District, Taizhou, 318000, Zhejiang, China

    Yaqiong Zhang, Zhaoyun Li, Hanjun Chen, Qianyi Zhong & Lingzhi Liang

  2. Taizhou Hospital, Taizhou, 318000, Zhejiang, China

    Meifang Chen

  3. Department of Ultrasound, Taizhou Municipal Hospital Affiliated to Medical College of Taizhou University, No. 381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang, China

    Bo Li

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  1. Yaqiong Zhang
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  4. Hanjun Chen
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Contributions

YZ, ZL, and BL contributed to the conception and design of this research. YZ, ZL, HC, MC, QZ, LL, and BL contributed to the drafting of the article and final approval of the submitted version. YZ, ZL, HC, MC, QZ, LL, and BL contributed to data analyses and the interpretation and completion of the figures and tables. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lingzhi Liang or Bo Li.

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The authors declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of The Cancer Genome Atlas Human Subjects Protection and Data Access Policies, adopted by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI).

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Informed consent was obtained from all individual participants included in the study.

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Zhang, Y., Li, Z., Chen, M. et al. lncRNA TCL6 correlates with immune cell infiltration and indicates worse survival in breast cancer. Breast Cancer 27, 573–585 (2020). https://doi.org/10.1007/s12282-020-01048-5

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  • DOI: https://doi.org/10.1007/s12282-020-01048-5

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