- Volume 15 Issue 6
DOI QR Code
Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer
- Qin, Jie-Jie ;
- Wang, Xiao-Rui ;
- Wang, Peng ;
- Ren, Peng-Fei ;
- Shi, Jian-Xiang ;
- Zhang, Hong-Fei ;
- Xia, Jun-Fen ;
- Wang, Kai-Juan ;
- Song, Chun-Hua ;
- Dai, Li-Ping ;
- Zhang, Jian-Ying
- Published : 2014.03.30
Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.
Esophageal cancer;tumor-associated antigen;autoantibody;diagnosis
- Wu J, Qiu T, Pan PT, et al (2011). Detection of serum anti-P53 antibodies from patients with colorectal cancer in China using a combination of P53- and phage-ELISA: correlation to clinical parameters. Asian Pac J Cancer Prev, 12, 2921-4.
- Zhang JY, Megleorino R, Peng XX, et al (2007). Antibody detection using tumor-associated antigen mini-array in diagnosing human hepatocellular carcinoma. J Hepatol, 46, 107-14.
- Zhang JY, Zhu W, Imai H, et al (2001). De-novo humoral immune responses to cancer-associated autoantigens during transition from chronic liver disease to hepatocellular carcinoma. Clin Exp Immunol, 125, 3-9. https://doi.org/10.1046/j.1365-2249.2001.01585.x
- Tan EM, Zhang J (2008). Autoantibodies to tumor- associated antigens: reporters from the immune system. Immunol Rev, 222, 328-40. https://doi.org/10.1111/j.1600-065X.2008.00611.x
- Wang X, Yu J, Sreekumar A, Varambally S, et al (2005). Autoantibody signatures in prostate cancer. N Engl J Med, 353, 1224-35. https://doi.org/10.1056/NEJMoa051931
- Winter SF, Minna JD, Johnson BE, et al (1992). Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res, 52, 4168-74.
- Ye H, Sun CQ, Ren PF, et al (2013). Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Oncol Lett, 5, 663-8.
- Zang J, Tan EM (2010). Autoantibodies to tumor- associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert Rev Mol Diagn, 10, 321-28. https://doi.org/10.1586/erm.10.12
- Zhang JT, Wang Kj, Zhang JZ (2011). Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma. J Proteome Res, 10, 2863-72. https://doi.org/10.1021/pr200141c
- Zhang JY (2007). Mini-array of tumor-associated antigens to enhance autoantibody detection for immunodiagnosis of hepatocellular carcinoma. Autoimmun Rev, 6, 143-8. https://doi.org/10.1016/j.autrev.2006.09.009
- Zhang JY, Casiano CA, Peng XX, et al (2003). Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens. Cancer Epidemiol Biomarkers Prev, 12, 136-43.
- Zhang JY, Chan EK, Peng XX, Tan EM (1999). A novel cytoplasmic protein with RNA- binding motifs is an autoantigen in human hepatocellular carcinoma. J Exp Med, 189, 1101-10. https://doi.org/10.1084/jem.189.7.1101
- Paradis V, Bedossa P (2007). In the new area of noninvasive markers of hepatocellular carcinoma. J Hepatol, 46, 9-11.
- Li LX, Wang KJ, Wang P, et al (2008). Detection of autoantibodies to multiple tumor-associated antigens in immunodiagnosis of ovarian cancer. Mol Med Rep, 1, 589-94.
- Liu W, Wang P, Li Z, et al (2009). Evaluation of tumourassociated antigen (TAA) miniarray in immunodiagnosis of colon cancer. Scand J Immunol, 69, 57-63. https://doi.org/10.1111/j.1365-3083.2008.02195.x
- Liu WH, Li Z, Wang P, et al (2006). Evaluation of diagnostic value on lung cancer using a panel of multiple tumorassociated antigens. Chin J Health Lab Technol, 16, 1412-14.
- Sang Y, Ma J, Huang RZ (2010). The development of clinical research on early diagnosis of esophageal cancer. China Prac Med, 5, 248-9.
- Soussi T (2000). p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res, 60, 1777-88.
- Tan EM (2001). Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis. J Clin Invest, 108, 1411-5. https://doi.org/10.1172/JCI14451
- Crawford LV, Pim DC, Bulbuook RD (1982). Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer, 30, 403-8. https://doi.org/10.1002/ijc.2910300404
- Anderson KS, Labaer J (2005). The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res, 4, 1123-33. https://doi.org/10.1021/pr0500814
- Chen WQ (2004). Assessing the validity and reliability of screening test. In: Epidemiology. Li LM, editors. Beijing: Publishing company of the people' health, 289-92.
- Chen Y, Huang XH, Shi HS, et al (2011). A novel and costeffective method for early lung cancer detection in immunized serum. Asian Pac J Cancer Prev, 12, 3009-12.
- Ersvaer E, Zhang JY, McCormack E, et al (2007). Cyclin B1 is commonly expressed in the cytoplasm of primary human acute myelogenous leukemia cells and serves as a leukemiaassociated antigen associated with autoantibody response in a subset of patients. Eur J Haematol, 79, 210-25. https://doi.org/10.1111/j.1600-0609.2007.00899.x
- Fang JQ, Sun ZQ. Normal distribution (2004). In: Biostatistics. Wang T, Qiu XQ, editors. Beijing: Publishing company of the people' health, 74-5.
- He J, Shao K (2011). The epidemiology, current status of management, challenge and future strategy for esophageal cancer in China. China Oncol, 21, 501-4.
- Himoto T, Kuriyama S, Zhang JY, et al (2005). Significance of autoantibodies against insulin-like growth factor II mRNA-binding proteins in 15 patients with hepatocellular carcinoma. Int J Oncol, 26, 311-7.
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Koziol JA, Zhang JY, Casiano CA, et al (2003). Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res, 9, 5120-6.
- Immunosignature: Serum Antibody Profiling for Cancer Diagnostics vol.16, pp.12, 2015, https://doi.org/10.7314/APJCP.2015.16.12.4833
- Clinical significance of serum autoantibodies against Ras-like GTPases, RalA, in patients with esophageal squamous cell carcinoma vol.13, pp.2, 2016, https://doi.org/10.1007/s10388-015-0510-8
- Diagnostic Value of the Survivin Autoantibody in Four Types of Malignancies vol.22, pp.6, 2018, https://doi.org/10.1089/gtmb.2017.0278
Supported by : National Natural Science Foundation of China