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

Breast Cancer. 2020 Jul;27(4):573-585. doi: 10.1007/s12282-020-01048-5. Epub 2020 Jan 20.

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.

Keywords: Breast cancer; Immune; Prognosis; TCL6; lncRNA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast / immunology
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Datasets as Topic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / metabolism*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • long noncoding RNA TCL6, human