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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Chemokine CCL27 is a novel plasma biomarker for identification the nasopharyngeal carcinoma patients from the Epstein-Barr virus capsid antigen-specific IgA seropositive population

Authors: Min-jie Mao, Ning Xue, Xue-ping Wang, Pei-dong Chi, Yi-jun Liu, Qi Huang, Shu-qin Dai, Wan-li Liu

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

To investigate the predictive value of chemokine CCL27 for identifying early stage nasopharyngeal carcinoma (NPC) patients within a population seropositive for Epstein-Barr virus (EBV) capsid antigen-specific IgA (VCA-IgA).

Methods

CCL27 in plasma samples from 104 NPC patients, 112 VCA-IgA–positive healthy donors, and 140 VCA-IgA–negative normal subjects was measured by ELISA. Expression of CCL27 in nasopharyngeal tissue from 20 VCA-IgA–positive healthy donors and 20 NPC patients was examined by immunohistochemical staining.

Results

Levels of CCL27 in the plasma of VCA-IgA–positive healthy donors (607.33 ± 218.81 pg/ml) were significantly higher than the levels in all NPC patients (437.09 ± 217.74, P = < 0.0001) and in the subset of patients with early stage NPC (463.85 ± 226.17, P = 0.0126). Plasma CCL27 levels were significantly lower in the VCA-IgA–negative normal subjects (358.22 ± 133.15 pg/ml) than in either the VCA-IgA–positive healthy donors (P < 0.0001) or the NPC patients (P = 0.0113). CCL27 protein was detected in 16 of 20 (80%) nasopharyngeal tissue samples from VCA-IgA–positive healthy donors and in 3 of 20 (15%) tumor tissue samples from NPC patients. There was no relationship between CCL27 levels and VCA-IgA titers or plasma EBV DNA content. Receiver operating characteristic (ROC) curves demonstrated that plasma CCL27 levels had a sensitivity of 67.00%, a specificity of 73.10%, and an area under the ROC of 0.725 (95% confidence interval [CI]: 0.657–0.793) for distinguishing between NPC patients and VCA-IgA–positive healthy donors. Further analysis showed that CCL27 levels could distinguish between early stage NPC patients and VCA-IgA–positive healthy donors with an area under the ROC of 0.712 (95% CI: 0.560–0.865), a sensitivity of 59.80%, and a specificity of 84.60%.

Conclusions

Chemokine CCL27 could successfully identify NPC patients within a VCA-IgA–positive population.
Literature
1.
go back to reference Han BL, XY X, Zhang CZ, JJ W, Han CF, Wang H, Wang X, Wang GS, Yang SJ, Xie Y. Systematic review on Epstein-Barr virus (EBV) DNA in diagnosis of nasopharyngeal carcinoma in Asian populations. Asian Pac J Cancer Prev. 2012;13(6):2577–81.CrossRefPubMed Han BL, XY X, Zhang CZ, JJ W, Han CF, Wang H, Wang X, Wang GS, Yang SJ, Xie Y. Systematic review on Epstein-Barr virus (EBV) DNA in diagnosis of nasopharyngeal carcinoma in Asian populations. Asian Pac J Cancer Prev. 2012;13(6):2577–81.CrossRefPubMed
2.
go back to reference ZJ X, Zheng RS, Zhang SW, Zou XN, Chen WQ. Nasopharyngeal carcinoma incidence and mortality in China in 2009. Chin J Cancer. 2013;32(8):453–60.CrossRef ZJ X, Zheng RS, Zhang SW, Zou XN, Chen WQ. Nasopharyngeal carcinoma incidence and mortality in China in 2009. Chin J Cancer. 2013;32(8):453–60.CrossRef
3.
go back to reference Lin TM, Yang CS, Chiou JF, SM T, Chen TY, YC T, Lin PJ, Kawamura AJ, Hirayama T. Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups. Am J Epidemiol. 1977;106(4):336–9.CrossRefPubMed Lin TM, Yang CS, Chiou JF, SM T, Chen TY, YC T, Lin PJ, Kawamura AJ, Hirayama T. Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups. Am J Epidemiol. 1977;106(4):336–9.CrossRefPubMed
4.
go back to reference Zeng Y, Zhang LG, Li HY, Jan MG, Zhang Q, YC W, Wang YS, GR S. Serological mass survey for early detection of nasopharyngeal carcinoma in Wuzhou City, China. Int J Cancer. 1982;29(2):139–41.CrossRefPubMed Zeng Y, Zhang LG, Li HY, Jan MG, Zhang Q, YC W, Wang YS, GR S. Serological mass survey for early detection of nasopharyngeal carcinoma in Wuzhou City, China. Int J Cancer. 1982;29(2):139–41.CrossRefPubMed
5.
go back to reference Pickard A, Chen CJ, Diehl SR, Liu MY, Cheng YJ, Hsu WL, Sun B, Hsu MM, Chen IH, Chen JY, et al. Epstein-Barr virus seroreactivity among unaffected individuals within high-risk nasopharyngeal carcinoma families in Taiwan. Int J Cancer. 2004;111(1):117–23.CrossRefPubMed Pickard A, Chen CJ, Diehl SR, Liu MY, Cheng YJ, Hsu WL, Sun B, Hsu MM, Chen IH, Chen JY, et al. Epstein-Barr virus seroreactivity among unaffected individuals within high-risk nasopharyngeal carcinoma families in Taiwan. Int J Cancer. 2004;111(1):117–23.CrossRefPubMed
6.
go back to reference Liu Z, Ji MF, Huang QH, Fang F, Liu Q, Jia WH, Guo X, Xie SH, Chen F, Liu Y, et al. Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in southern China. Am J Epidemiol. 2013;177(3):242–50.CrossRefPubMed Liu Z, Ji MF, Huang QH, Fang F, Liu Q, Jia WH, Guo X, Xie SH, Chen F, Liu Y, et al. Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in southern China. Am J Epidemiol. 2013;177(3):242–50.CrossRefPubMed
7.
go back to reference Luo J, Chia KS, Chia SE, Reilly M, Tan CS, Ye W. Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese populations, 1973-1997. Eur J Epidemiol. 2007;22(8):513–21.CrossRefPubMed Luo J, Chia KS, Chia SE, Reilly M, Tan CS, Ye W. Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese populations, 1973-1997. Eur J Epidemiol. 2007;22(8):513–21.CrossRefPubMed
8.
go back to reference Liu Y, Huang Q, Liu W, Liu Q, Jia W, Chang E, Chen F, Liu Z, Guo X, Mo H, et al. Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China. Int J Cancer. 2012;131(2):406–16.CrossRefPubMed Liu Y, Huang Q, Liu W, Liu Q, Jia W, Chang E, Chen F, Liu Z, Guo X, Mo H, et al. Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China. Int J Cancer. 2012;131(2):406–16.CrossRefPubMed
10.
11.
12.
go back to reference Thangavadivel S, Zelle-Rieser C, Olivier A, Postert B, Untergasser G, Kern J, Brunner A, Gunsilius E, Biedermann R, Hajek R, et al. CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma. Oncotarget. 2016;7(48):78605–18. Thangavadivel S, Zelle-Rieser C, Olivier A, Postert B, Untergasser G, Kern J, Brunner A, Gunsilius E, Biedermann R, Hajek R, et al. CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma. Oncotarget. 2016;7(48):78605–18.
13.
go back to reference Huang V, Lonsdorf AS, Fang L, Kakinuma T, Lee VC, Cha E, Zhang H, Nagao K, Zaleska M, Olszewski WL, et al. Cutting edge: rapid accumulation of epidermal CCL27 in skin-draining lymph nodes following topical application of a contact sensitizer recruits CCR10-expressing T cells. J Immunol. 2008;180(10):6462–6.CrossRefPubMed Huang V, Lonsdorf AS, Fang L, Kakinuma T, Lee VC, Cha E, Zhang H, Nagao K, Zaleska M, Olszewski WL, et al. Cutting edge: rapid accumulation of epidermal CCL27 in skin-draining lymph nodes following topical application of a contact sensitizer recruits CCR10-expressing T cells. J Immunol. 2008;180(10):6462–6.CrossRefPubMed
14.
go back to reference Wani SQ, Khan T, Wani SY, Mir LR, Lone MM, Malik TR, Najmi AM, Afroz F, Teli MA, Khan NA. Nasopharyngeal carcinoma: a 15 year study with respect to Clinicodemography and survival analysis. Indian J Otolaryngol Head Neck Surg. 2016;68(4):511–21.CrossRefPubMedPubMedCentral Wani SQ, Khan T, Wani SY, Mir LR, Lone MM, Malik TR, Najmi AM, Afroz F, Teli MA, Khan NA. Nasopharyngeal carcinoma: a 15 year study with respect to Clinicodemography and survival analysis. Indian J Otolaryngol Head Neck Surg. 2016;68(4):511–21.CrossRefPubMedPubMedCentral
15.
go back to reference Zhang J, Shu C, Song Y, Li Q, Huang J, Ma X. Epstein-Barr virus DNA level as a novel prognostic factor in nasopharyngeal carcinoma: a meta-analysis. Medicine (Baltimore). 2016;95(40):e5130.CrossRef Zhang J, Shu C, Song Y, Li Q, Huang J, Ma X. Epstein-Barr virus DNA level as a novel prognostic factor in nasopharyngeal carcinoma: a meta-analysis. Medicine (Baltimore). 2016;95(40):e5130.CrossRef
16.
go back to reference Tang LQ, Chen QY, Fan W, Liu H, Zhang L, Guo L, Luo DH, Huang PY, Zhang X, Lin XP, et al. Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein-Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging. J Clin Oncol. 2013;31(23):2861–9.CrossRefPubMed Tang LQ, Chen QY, Fan W, Liu H, Zhang L, Guo L, Luo DH, Huang PY, Zhang X, Lin XP, et al. Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein-Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging. J Clin Oncol. 2013;31(23):2861–9.CrossRefPubMed
17.
go back to reference Le QT, Zhang Q, Cao H, Cheng AJ, Pinsky BA, Hong RL, Chang JT, Wang CW, Tsao KC, Lo YD, et al. An international collaboration to harmonize the quantitative plasma Epstein-Barr virus DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma. Clin Cancer Res. 2013;19(8):2208–15.CrossRefPubMedPubMedCentral Le QT, Zhang Q, Cao H, Cheng AJ, Pinsky BA, Hong RL, Chang JT, Wang CW, Tsao KC, Lo YD, et al. An international collaboration to harmonize the quantitative plasma Epstein-Barr virus DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma. Clin Cancer Res. 2013;19(8):2208–15.CrossRefPubMedPubMedCentral
18.
go back to reference KJ Y, Hsu WL, Pfeiffer RM, Chiang CJ, Wang CP, Lou PJ, Cheng YJ, Gravitt P, Diehl SR, Goldstein AM, et al. Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. Clin Cancer Res. 2011;17(7):1906–14.CrossRef KJ Y, Hsu WL, Pfeiffer RM, Chiang CJ, Wang CP, Lou PJ, Cheng YJ, Gravitt P, Diehl SR, Goldstein AM, et al. Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. Clin Cancer Res. 2011;17(7):1906–14.CrossRef
19.
go back to reference Simonetti O, Goteri G, Lucarini G, Filosa A, Pieramici T, Rubini C, Biagini G, Offidani A. Potential role of CCL27 and CCR10 expression in melanoma progression and immune escape. Eur J Cancer. 2006;42(8):1181–7.CrossRefPubMed Simonetti O, Goteri G, Lucarini G, Filosa A, Pieramici T, Rubini C, Biagini G, Offidani A. Potential role of CCL27 and CCR10 expression in melanoma progression and immune escape. Eur J Cancer. 2006;42(8):1181–7.CrossRefPubMed
20.
go back to reference Kagami S, Sugaya M, Minatani Y, Ohmatsu H, Kakinuma T, Fujita H, Tamaki K. Elevated serum CTACK/CCL27 levels in CTCL. J INVEST DERMATOL. 2006;126(5):1189–91.CrossRefPubMed Kagami S, Sugaya M, Minatani Y, Ohmatsu H, Kakinuma T, Fujita H, Tamaki K. Elevated serum CTACK/CCL27 levels in CTCL. J INVEST DERMATOL. 2006;126(5):1189–91.CrossRefPubMed
21.
go back to reference Martinez-Rodriguez M, Thompson AK, Monteagudo C. High CCL27 immunoreactivity in 'supratumoral' epidermis correlates with better prognosis in patients with cutaneous malignant melanoma. J Clin Pathol. 2017;70(1):15–19. Martinez-Rodriguez M, Thompson AK, Monteagudo C. High CCL27 immunoreactivity in 'supratumoral' epidermis correlates with better prognosis in patients with cutaneous malignant melanoma. J Clin Pathol. 2017;70(1):15–19.
22.
go back to reference Pivarcsi A, Muller A, Hippe A, Rieker J, van Lierop A, Steinhoff M, Seeliger S, Kubitza R, Pippirs U, Meller S, et al. Tumor immune escape by the loss of homeostatic chemokine expression. Proc Natl Acad Sci U S A. 2007;104(48):19055–60.CrossRefPubMedPubMedCentral Pivarcsi A, Muller A, Hippe A, Rieker J, van Lierop A, Steinhoff M, Seeliger S, Kubitza R, Pippirs U, Meller S, et al. Tumor immune escape by the loss of homeostatic chemokine expression. Proc Natl Acad Sci U S A. 2007;104(48):19055–60.CrossRefPubMedPubMedCentral
23.
go back to reference Khaiboullina SF, Gumerova AR, Khafizova IF, Martynova EV, Lombardi VC, Bellusci S, Rizvanov AA. CCL27: novel cytokine with potential role in pathogenesis of multiple sclerosis. Biomed Res Int. 2015;2015:189638.CrossRefPubMedPubMedCentral Khaiboullina SF, Gumerova AR, Khafizova IF, Martynova EV, Lombardi VC, Bellusci S, Rizvanov AA. CCL27: novel cytokine with potential role in pathogenesis of multiple sclerosis. Biomed Res Int. 2015;2015:189638.CrossRefPubMedPubMedCentral
24.
go back to reference Chen Y, Xin X, Cui Z, Zheng Y, Guo J, Chen Y, Lin Y, Su G. Diagnostic value of serum Epstein-Barr virus Capsid antigen-IgA for nasopharyngeal carcinoma: a meta-analysis based on 21 studies. Clin Lab. 2016;62(6):1155–66.PubMed Chen Y, Xin X, Cui Z, Zheng Y, Guo J, Chen Y, Lin Y, Su G. Diagnostic value of serum Epstein-Barr virus Capsid antigen-IgA for nasopharyngeal carcinoma: a meta-analysis based on 21 studies. Clin Lab. 2016;62(6):1155–66.PubMed
25.
go back to reference Shao JY, Li YH, Gao HY, QL W, Cui NJ, Zhang L, Cheng G, LF H, Ernberg I, Zeng YX. Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin a/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma. CANCER-AM CANCER SOC. 2004;100(6):1162–70. Shao JY, Li YH, Gao HY, QL W, Cui NJ, Zhang L, Cheng G, LF H, Ernberg I, Zeng YX. Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin a/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma. CANCER-AM CANCER SOC. 2004;100(6):1162–70.
26.
go back to reference Henle G, Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer. 1976;17(1):1–7.CrossRefPubMed Henle G, Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer. 1976;17(1):1–7.CrossRefPubMed
27.
go back to reference Lo YM, Chan LY, Chan AT, Leung SF, Lo KW, Zhang J, Lee JC, Hjelm NM, Johnson PJ, Huang DP. Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. Cancer Res. 1999;59(21):5452–5.PubMed Lo YM, Chan LY, Chan AT, Leung SF, Lo KW, Zhang J, Lee JC, Hjelm NM, Johnson PJ, Huang DP. Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. Cancer Res. 1999;59(21):5452–5.PubMed
28.
go back to reference Zhang C, Zong Y, Huang B, Sun Y, Ye Y, Feng K, Li J, Zhang F. Enhancing the efficiency of Epstein-Barr viral serologic test in the diagnosis of nasopharyngeal carcinoma. Zhonghua Zhong Liu Za Zhi. 2002;24(4):356–9.PubMed Zhang C, Zong Y, Huang B, Sun Y, Ye Y, Feng K, Li J, Zhang F. Enhancing the efficiency of Epstein-Barr viral serologic test in the diagnosis of nasopharyngeal carcinoma. Zhonghua Zhong Liu Za Zhi. 2002;24(4):356–9.PubMed
Metadata
Title
Chemokine CCL27 is a novel plasma biomarker for identification the nasopharyngeal carcinoma patients from the Epstein-Barr virus capsid antigen-specific IgA seropositive population
Authors
Min-jie Mao
Ning Xue
Xue-ping Wang
Pei-dong Chi
Yi-jun Liu
Qi Huang
Shu-qin Dai
Wan-li Liu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3718-2

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