Combination of autoantibodies against NY‑ESO‑1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma

Peng,Yu‑Hui; Xu,Yi‑Wei; Qiu,Si‑Qi; Hong,Chao‑Qun; Zhai,Tian‑Tian; Li,En‑Min; Xu,Li‑Yan

doi:10.3892/ol.2014.2286

Combination of autoantibodies against NY‑ESO‑1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma

Authors:
- Yu‑Hui Peng
- Yi‑Wei Xu
- Si‑Qi Qiu
- Chao‑Qun Hong
- Tian‑Tian Zhai
- En‑Min Li
- Li‑Yan Xu
View Affiliations

Affiliations: Department of Clinical Laboratory, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, The Breast Center, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Oncological Research Lab, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
Published online on: June 25, 2014 https://doi.org/10.3892/ol.2014.2286
Pages: 1096-1102

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY‑ESO‑1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY‑ESO‑1 and classical Epstein‑Barr virus marker, viral capsid antigen immunoglobulin A (VCA‑IgA), were measured by enzyme‑linked immunosorbent assay. Measurement of autoantibodies against NY‑ESO‑1 and VCA‑IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7‑52.6/89.4‑97.8%] and 55.4/95.7% (95% CI, 45.7‑64.7/90.4‑98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY‑ESO‑1 (0.821; 95% CI, 0.771‑0.871) was marginally lower than that for VCA‑IgA (0.860; 95% CI, 0.810‑0.910) in NPC. The combination of autoantibodies against NY‑ESO‑1 and VCA‑IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6‑87.0%) and a specificity of 90.6% (95% CI, 84.1‑94.7%). Moreover, detection of autoantibodies against NY‑ESO‑1 could differentiate early‑stage NPC patients from normal controls. Our results suggest that autoantibodies against NY‑ESO‑1 may serve as a potential biomarker, as a supplement to VCA‑IgA, for the screening and diagnosis of NPC.

View Figures

View References

1	Razak AR, Siu LL, Liu FF, et al: Nasopharyngeal carcinoma: the next challenges. Eur J Cancer. 46:1967–1978. 2010.
2	Yu MC and Yuan JM: Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 12:421–429. 2002.
3	Cao XP, Lu TX, Ye WJ and Cui NJ: Prospective study on long-term efficacy of external plus intracavitary radiotherapy on stage I–II nasopharyngeal carcinoma. Ai Zheng. 26:204–207. 2007.(In Chinese).
4	Chen Y, Sun Y, Liang SB, et al: Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China. Cancer. 119:2230–2238. 2013.
5	Chan KH, Gu YL, Ng F, et al: EBV specific antibody-based and DNA-based assays in serologic diagnosis of nasopharyngeal carcinoma. Int J Cancer. 105:706–709. 2003.
6	Low WK, Leong JL, Goh YH and Fong KW: Diagnostic value of Epstein-Barr viral serology in nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 123:505–507. 2000.
7	Tsang RK, Vlantis AC, Ho RW, et al: Sensitivity and specificity of Epstein-Barr virus IGA titer in the diagnosis of nasopharyngeal carcinoma: a three-year institutional review. Head Neck. 26:598–602. 2004.
8	Gallagher A, Armstrong AA, MacKenzie J, et al: Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin’s disease. Int J Cancer. 84:442–448. 1999.
9	Lei KI, Chan LY, Chan WY, Johnson PJ and Lo YM: Diagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T-cell lymphoma. Clin Cancer Res. 8:29–34. 2002.
10	Chapman C, Murray A, Chakrabarti J, et al: Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 18:868–873. 2007.
11	Boyle P, Chapman CJ, Holdenrieder S, et al: Clinical validation of an autoantibody test for lung cancer. Ann Oncol. 22:383–389. 2011.
12	Chang W, Wu L, Cao F, et al: Development of autoantibody signatures as biomarkers for early detection of colorectal carcinoma. Clin Cancer Res. 17:5715–5724. 2011.
13	Zayakin P, Ancāns G, Siliņa K, et al: Tumor-associated autoantibody signature for the early detection of gastric cancer. Int J Cancer. 132:137–147. 2013.
14	Liu H, Zhang J, Wang S, et al: Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system. Cancer Epidemiol. 36:82–88. 2012.
15	Tong YQ, Liu B, Huang J, et al: BMI-1 autoantibody in serum as a new potential biomarker of nasopharyngeal carcinoma. Cancer Biol Ther. 7:340–344. 2008.
16	Brass N, Rácz A, Bauer C, et al: Role of amplified genes in the production of autoantibodies. Blood. 93:2158–2166. 1999.
17	Jäger D, Stockert E, Güre AO, et al: Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Cancer Res. 61:2055–2061. 2001.
18	Tan EM: Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis. J Clin Invest. 108:1411–1415. 2001.
19	Finn OJ: Immune response as a biomarker for cancer detection and a lot more. N Engl J Med. 353:1288–1290. 2005.
20	Qiu J, Choi G, Li L, et al: Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. J Clin Oncol. 26:5060–5066. 2008.
21	Robbins PF, Morgan RA, Feldman SA, et al: Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 29:917–924. 2011.
22	Jäger E, Nagata Y, Gnjatic S, et al: Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA. 97:4760–4765. 2000.
23	Gnjatic S, Nishikawa H, Jungbluth AA, et al: NY-ESO-1: review of an immunogenic tumor antigen. Adv Cancer Res. 95:1–30. 2006.
24	Chapman CJ, Murray A, McElveen JE, et al: Autoantibodies in lung cancer: possibilities for early detection and subsequent cure. Thorax. 63:228–233. 2008.
25	Gati A, Lajmi N, Derouiche A, et al: NY-ESO-1 expression and immunogenicity in prostate cancer patients. Tunis Med. 89:779–783. 2011.
26	Chen L, Mao YP, Xie FY, et al: The seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma is prognostically useful for patients treated with intensity-modulated radiotherapy from an endemic area in China. Radiother Oncol. 104:331–337. 2012.
27	Fang Qiang-Ji, Hu Liang-Ping and Zhao Nai-Qing: Binomial distribution. Statistical Methods for Biomedical Research. 1st edition. Higher Education Press; Beijing: pp. 462007
28	Chapman CJ, Thorpe AJ, Murray A, et al: Immunobiomarkers in small cell lung cancer: potential early cancer signals. Clin Cancer Res. 17:1474–1480. 2011.
29	Rodolfo M, Luksch R, Stockert E, et al: Antigen-specific immunity in neuroblastoma patients: antibody and T-cell recognition of NY-ESO-1 tumor antigen. Cancer Res. 63:6948–6955. 2003.
30	Zhong L, Coe SP, Stromberg AJ, et al: Profiling tumor-associated antibodies for early detection of non-small cell lung cancer. J Thorac Oncol. 1:513–519. 2006.
31	Fernández Madrid F: Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett. 230:187–198. 2005.
32	Türeci O, Mack U, Luxemburger U, et al: Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1. Cancer Lett. 236:64–71. 2006.
33	Chang KP, Hao SP, Chang JH, et al: Macrophage inflammatory protein-3alpha is a novel serum marker for nasopharyngeal carcinoma detection and prediction of treatment outcomes. Clin Cancer Res. 14:6979–6987. 2008.