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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 8  |  Page : 180-183

Association of toll-like receptors with the risk of oral squamous cell carcinoma


1 Department of Oral and Maxillofacial Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
2 Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

Date of Web Publication26-Mar-2018

Correspondence Address:
Xiang-Bo Kong
Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.163789

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 > Abstract 


Aim of Study: Association of toll-like receptors (TLRs) with the risk of oral squamous cell carcinoma (OSCC) from the published reports is still conflicting. This study was conducted to evaluate the relationship between TLRs and the risk of OSCC using meta-analysis method.
Materials and Methods: The association studies were identified from PubMed and Cochrane Library on April 01 2015, and eligible investigations were included and synthesized using meta-analysis method.
Result: Three reports were recruited into this meta-analysis for the association of TLRs with OSCC susceptibility. In this meta-analysis, we found that TLRs were not associated with OSCC susceptibility. However, in the sub-group analysis, we found that TLR-7 was associated with OSCC risk.
Conclusion: TLR-7 was associated with OSCC risk. TLR-7 might be an indicator to predict the OSCC risk. However, more studies should be conducted to confirm it.

Keywords: Meta-analysis, oral squamous cell carcinoma, toll-like receptors


How to cite this article:
Fang SL, Kong XB, Zhang ZQ. Association of toll-like receptors with the risk of oral squamous cell carcinoma. J Can Res Ther 2018;14:180-3

How to cite this URL:
Fang SL, Kong XB, Zhang ZQ. Association of toll-like receptors with the risk of oral squamous cell carcinoma. J Can Res Ther [serial online] 2018 [cited 2018 Apr 26];14:180-3. Available from: http://www.cancerjournal.net/text.asp?2018/14/8/180/163789




 > Introduction Top


Toll-like receptors (TLRs) are important innate immune proteins, and the activation of the TLRs results in the activation of intracellular signaling pathways, leading to the proinflammatory cytokines expression that are essential to the identification and clearance of invading pathogens.[1],[2] In addition to conserved pathogenic components, endogenous danger signals created upon tissue damage are also sensed by TLRs, and detection of these types of stimuli results in TLR mediated inflammation that is vital to fight pathogenic invasion and drive tissue repair.[3]

Oral squamous cell carcinoma (OSCC) constitutes 3% of all cancers with predominant occurrence in middle-aged and elderly males.[4] Tumor recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines are associated with the onset of OSCC.[4] Cell proliferation is a major underlying cause of mortality amongst patients with OSCC.[5]

Most of the epidemiologic investigations studyingthe relationship between TLRs and the OSCC risk were conducted in the past decades. However, the available evidence is weak due to the sparseness of data or disagreements among the reported investigations. There was no other meta-analysis to investigate the association of TLRs with the OSCC risk. This systemic review and meta-analysis were performed to investigate whether the TLRs were associated with the risk of OSCC.


 > Materials and Methods Top



 > Search Strategy for the Relationship between Toll-Like Receptors and the Risk of Oral Squamous Cell Carcinoma Top


The relevant studies were searched from the electronic databases of PubMed and Cochrane Library on April 01 2014. The retrieval strategy of (toll-like receptors or TLRs or TLR) and (oral squamous cell carcinoma or OSCC) was entered into these databases. The additional reports were identified through references cited in recruited articles.

Inclusion and exclusion criteria

Inclusion criteria

  1. The outcome had to be OSCC
  2. There had to be at least two comparison groups (OSCC group vs. control group)
  3. Investigation should provide the rate of TLRs expression.


Exclusion criteria

  1. Review articles and editorials
  2. Case reports
  3. Preliminary result not on TLRs or outcome
  4. If multiple publications for the same data from the same study group occurred, we only recruited the later paper into our final analysis.


Data extraction and synthesis

The following information from each eligible study was extracted independently by two investigators: First author's surname, year of publication, location of the study performed, control source of the control group, and the number of cases and controls for positive TLRs. The results were compared, and disagreement was resolved by discussion.

Statistical analysis

Cochrane Review Manager version 5 (Cochrane Library, UK) was used to calculate the available data from each study. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the P value of heterogeneity test was <0.1.[6],[7] Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated.

P < 0.05 was required for the pooled OR to be statistically significant.[8],[9]I2 was used to test the heterogeneity among the included studies.


 > Results Top


Study characteristics

Three studies [10],[11],[12] reporting the relationship between TLRs and OSCC susceptibility were recruited into this meta-analysis [Table 1]. The data of our interest were extracted [Table 1]. Two studies [10],[11] were for TLR-4, one study [12] was for TLR-7, and one study [10] was for TLR-9.
Table 1: Characteristics of the studies evaluating the effects of toll-like receptors on the risk of oral squamous cell carcinoma

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Association of toll-like receptors with oral squamous cell carcinoma susceptibility

In this meta-analysis, we found that TLRs were not associated with OSCC susceptibility [OR = 9.86, 95% CI: 3.75–25.95, P < 0.00001; [Figure 1] and [Table 2].
Figure 1: Association of toll-like receptors with oral squamous cell carcinoma risk

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Table 2: Meta analysis of association of toll-like receptors with oral squamous cell carcinoma risk

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Association of toll-like receptors-4 with oral squamous cell carcinoma susceptibility

In this meta-analysis, we found that TLR-4 was not associated with OSCC susceptibility [OR = 3.91, 95% CI: 0.59–25.87, P= 0.16; [Figure 1] and [Table 2].

Association of toll-like receptors-7 with oral squamous cell carcinoma susceptibility

TLR-7 was associated with OSCC susceptibility [OR = 63.53, 95% CI: 3.78–1068.63, P= 0.004; [Figure 1] and [Table 2].

Association of toll-like receptors-9 with oral squamous cell carcinoma susceptibility

TLR-9 was not associated with OSCC susceptibility [OR = 2.86, 95% CI: 0.63–12.92, P= 0.17; [Figure 1] and [Table 2].


 > Discussion Top


In this systemic review and meta-analysis, there were three included studies for this meta-analysis, and the results indicated that TLRs were not associated with OSCC risk. Interestingly, in the sub-group analysis, TLR-7 was associated with OSCC risk. In order to explore whether the TLR-7 is an indicator to predict the onset of OSCC, more studies for the association between TLR-7 and OSCC risk should be performed in the future.

Sun et al.[13] suggested that TLR4 was functionally expressed in human OSCC cells, and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might, thus, elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC. Ren et al.[14] demonstrated that the expression of TLR-4 was increased in OSCC and that high level of TLR4 expression was associated with a short survival rate.

Min et al.[15] performed a study and showed that TLR-9 expression level was higher in OSCC tissues than in paired adjacent normal tissues, and the expression level of TLR-9 was significantly associated with tumor size, tumor clinical stage, and Ki-67 expression. Kauppila et al.[16] reported that TLR-9 mediates OTSCC invasion and migration in vitro and is an independent prognostic factor of OTSCC, and inhibition of TLR-9 may be a novel therapeutic opportunity in oral cancer. Furthermore, activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity.[17] Mäkinen et al.[18] found that TLRs showed high expression in early-stage OTSCC and TLR-2, -4, and -9 seemed to predict invasive tumor growth.

There was no other meta-analysis to investigate the association of TLRs with the OSCC risk. In our meta-analysis, TLRs were not associated with OSCC susceptibility, and TLR-7 was associated with OSCC risk. However, the number of included studies was small. The conclusion might be less robust, and more studies should be performed in the future.


 > Conclusion Top


TLRs were not associated with OSCC susceptibility, and TLR-7 was associated with OSCC risk. However, more studies should be conducted to confirm it.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Kropp KA, Hsieh WY, Isern E, Forster T, Krause E, Brune W, et al. A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional activation pathways upon acute infection. PLoS Pathog 2015;11:e1004737.  Back to cited text no. 1
[PUBMED]    
2.
Xiang W, Chao ZY, Feng DY. Role of Toll-like receptor/MYD88 signaling in neurodegenerative diseases. Rev Neurosci 2015; Doi:10.1515/revneuro-2014-0067. Available from: http://www.ncbi.nlm.nih.gov/pubmed/?term=25870959. [Last accessed on 2015 Jul 31].  Back to cited text no. 2
    
3.
Bryant CE, Gay NJ, Heymans S, Sacre S, Schaefer L, Midwood KS. Advances in Toll-like receptor biology: Modes of activation by diverse stimuli. Crit Rev Biochem Mol Biol 2015:1-21. Doi:10.3109/10409238.2015.1033511. Available from: http://www.ncbi.nlm.nih.gov/pubmed/?term=25857820. [Last accessed on 2015 Jul 31].  Back to cited text no. 3
    
4.
Skrinjar I, Brailo V, Vidovic-Juras D, Vucicevic-Boras V, Milenovic A. Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2015;20:e402-7.  Back to cited text no. 4
[PUBMED]    
5.
Liu G, Ren X, Gao C, Zhang W. Acylglycerol kinase promotes the proliferation and cell cycle progression of oral squamous cell carcinoma. Mol Med Rep 2015;12:2225-30.  Back to cited text no. 5
[PUBMED]    
6.
Zhou TB, Drummen GP, Jiang ZP, Long YB, Qin YH. Association of peroxisome proliferator-activated receptors/retinoic acid receptors with renal diseases. J Recept Signal Transduct Res 2013;33:349-52.  Back to cited text no. 6
[PUBMED]    
7.
Zhou TB, Qin YH, Su LN, Lei FY, Huang WF, Zhao YJ, et al. The association between angiotensin-converting enzyme insertion/deletion gene variant and risk of focal segmental glomerulosclerosis: A systematic review and meta-analysis. J Renin Angiotensin Aldosterone Syst 2011;12:624-33.  Back to cited text no. 7
[PUBMED]    
8.
Zhou TB, Qin YH, Su LN, Lei FY, Huang WF, Zhao YJ. ACE I/D gene polymorphism can't predict the steroid responsiveness in Asian children with idiopathic nephrotic syndrome: A meta-analysis. PLoS One 2011;6:e19599.  Back to cited text no. 8
[PUBMED]    
9.
Zhou TB, Yin SS, Jiang ZP. Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease. J Recept Signal Transduct Res 2013;33:325-31.  Back to cited text no. 9
[PUBMED]    
10.
Kotrashetti VS, Nayak R, Bhat K, Hosmani J, Somannavar P. Immunohistochemical expression of TLR4 and TLR9 in various grades of oral epithelial dysplasia and squamous cell carcinoma, and their roles in tumor progression: A pilot study. Biotech Histochem 2013;88:311-22.  Back to cited text no. 10
[PUBMED]    
11.
Nair S, Kotrashetti VS, Nayak R, Bhat K, Somannavar P, Hosmani J. HSP70 induces TLR4 signaling in oral squamous cell carcinoma: An immunohistochemical study. J Cancer Res Ther 2013;9:624-9.  Back to cited text no. 11
[PUBMED]    
12.
Ni YH, Ding L, Zhang DY, Hou YY, Huang X, Hu Q. Distinct expression patterns of Toll-like receptor 7 in tumour cells and fibroblast-like cells in oral squamous cell carcinoma. Histopathology 2015; Doi: 10.1111/his.12703. Available from: http://www.ncbi.nlm.nih.gov/pubmed/?term=25828894. [Last accessed on 2015 Jul 31].  Back to cited text no. 12
    
13.
Sun Z, Luo Q, Ye D, Chen W, Chen F. Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis. Mol Cancer 2012;11:33.  Back to cited text no. 13
[PUBMED]    
14.
Ren WH, Zhang LM, Liu HQ, Gao L, Chen C, Qiang C, et al. Protein overexpression of CIRP and TLR4 in oral squamous cell carcinoma: An immunohistochemical and clinical correlation analysis. Med Oncol 2014;31:120.  Back to cited text no. 14
[PUBMED]    
15.
Min R, Zun Z, Siyi L, Wenjun Y, Lizheng W, Chenping Z. Increased expression of Toll-like receptor-9 has close relation with tumour cell proliferation in oral squamous cell carcinoma. Arch Oral Biol 2011;56:877-84.  Back to cited text no. 15
[PUBMED]    
16.
Kauppila JH, Korvala J, Siirilä K, Manni M, Mäkinen LK, Hagström J, et al. Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue. J Oral Pathol Med 2014; Doi: 10.1111/jop.12272. Available from: http://www.ncbi.nlm.nih.gov/pubmed/?term=25338738. [Last accessed on 2015 Jul 31].  Back to cited text no. 16
    
17.
Ruan M, Zhang Z, Li S, Yan M, Liu S, Yang W, et al. Activation of Toll-like receptor-9 promotes cellular migration via up-regulating MMP-2 expression in oral squamous cell carcinoma. PLoS One 2014;9:e92748.  Back to cited text no. 17
[PUBMED]    
18.
Mäkinen LK, Atula T, Häyry V, Jouhi L, Datta N, Lehtonen S, et al. Predictive role of Toll-like receptors 2, 4, and 9 in oral tongue squamous cell carcinoma. Oral Oncol 2015;51:96-102.  Back to cited text no. 18
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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