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. 2017 Sep 1:10:4339-4346.
doi: 10.2147/OTT.S136194. eCollection 2017.

Toll-like receptors 7 and 8 expression correlates with the expression of immune biomarkers and positively predicts the clinical outcome of patients with melanoma

Moucheng Zhang  1   2   3 , Zhilong Yan  2 , Junjiang Wang  1   3 , Xueqing Yao  1   3
Affiliations

Toll-like receptors 7 and 8 expression correlates with the expression of immune biomarkers and positively predicts the clinical outcome of patients with melanoma

Moucheng Zhang et al. Onco Targets Ther. .

Erratum in

Abstract

Background: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression.

Methods: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234. Log rank (Mantel-Cox) tests were used to perform survival analysis. Multivariate survival analysis was performed on a Cox-regression hazard model. Spearman correlation analyses were used to address the relationship between the expressions of TLR7/8 levels and immune biomarkers in melanoma tumors.

Results: Survival analysis suggested that high levels of TLR7 or TLR8 expression predicted better clinical outcome for melanoma patients (TLR7: HR =1.734, P<0.0001; TLR8: HR =2.072, P<0.0001). Moreover, multivariate survival analysis implicated TLR7 as a prognostic factor independent of age, gender, or pathological stage. Further analysis demonstrated that expression levels of TLR7/8 strongly correlated with that of dendritic cell markers and chemokines/chemokine receptors, including CCR2, CCR5, CCL3, and CCL5. Importantly, expression levels of both TLR7 and TLR8 were also highly correlated with the expressions of CD8 and other functional markers of CD8+ T cells.

Conclusion: High gene expression of TLR7 and TLR8 in melanoma tumors is associated with high expression levels of functional markers of immune cells, which predicts longer overall survival of patients with melanoma. Our results not only provide an important reference for the clinical prognosis of melanoma but also present new implications for the design of melanoma immunotherapy.

Keywords: TLR7; TLR8; immune marker; immunotherapy; melanoma; prognosis; survival.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Transcriptional levels of TLR7 and TLR8 predict the clinical outcome of patients with melanoma. Survival analysis of melanoma patients (TCGA database) is shown with high and low expressions of TLR7 (A) and TLR8 (B). Survival analysis of melanoma patients (GSE19234) is shown with high and low expressions of TLR7 (C) and TLR8 (D). The patients were divided into two groups based on the median mRNA expression levels of TLR7 and TLR8. Abbreviations: TLR, Toll-like receptor; TCGA, The Cancer Genome Atlas.
Figure 2
Figure 2
Correlation analysis between expressions of TLR7 and factors associated with dendritic cells (DC). Correlation analysis between (A) TLR7 and ITGAM, (B) TLR7 and ITGAX, (C) TLR7 and IFNB, and (D) TLR7 and IRF3. Note: r, Pearson’s correlation coefficient. Abbreviations: TLR, Toll-like receptor; IRF3, interferon regulatory factor 3; IFNB, interferon B.
Figure 3
Figure 3
Correlation analysis between expressions of TLR7 and chemokines and their receptors. Correlation analysis between (A) TLR7 and CCR2, (B) TLR7 and CCR5, (C) TLR7 and CCL2, and (D) TLR7 and CCL5. Note: r, Pearson’s correlation coefficient. Abbreviation: TLR, Toll-like receptor.
Figure 4
Figure 4
Correlation analysis between expression levels of TLR7 and CD8+ cytotoxic T-cell markers. Correlation analysis between (A) TLR7 and CD8A, (B) TLR7 and IFNG, (C) TLR7 and GZMB, and (D) TLR7 and PRF1. Note: r, Pearson’s correlation coefficient. Abbreviations: TLR, Toll-like receptor; IFNG, interferon gamma.
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