Cancer Medicine (Aug 2019)

MGMT autoantibodies as a potential prediction of recurrence and treatment response biomarker for glioma patients

  • Haibin Wu,
  • Zhitong Deng,
  • Hao Wang,
  • Xuetao Li,
  • Ting Sun,
  • Zhennan Tao,
  • Lin Yao,
  • Yanping Jin,
  • Xiaoying Wang,
  • Lan Yang,
  • Hongwei Ma,
  • Yulun Huang,
  • Youxin Zhou,
  • Ziwei Du

DOI
https://doi.org/10.1002/cam4.2346
Journal volume & issue
Vol. 8, no. 9
pp. 4359 – 4369

Abstract

Read online

Abstract Background Cancer‐specific autoantibodies found in serum of cancer patients have been characterized as potential predictors of the high risk of recurrence and treatment response. The objective of this study is to investigate the clinical utility of serum O‐6‐methylguanine‐DNA methyltransferase (MGMT) autoantibodies as novel biomarkers for prediction of recurrence and treatment response for glioma through MGMT peptides microarray. Methods A total of 201 serum samples of glioma patients with various WHO grade and 311 serum samples of healthy donors were examined for the detection of MGMT autoantibodies by peptides microarray. The clinical value of MGMT autoantibodies was studied through univariable and multivariable analyses. Results Autoantibodies to MGMT peptides were detected in sera from glioma patients and five highly responsive autoantibodies to peptides were identified in the glioma group. The positive rate of MGMT autoantibody to 20 peptides in glioma groups is compared with healthy individuals, the positive rate of MGMT‐02 (45%), MGMT‐04 (27%), MGMT‐07 (21%), MGMT‐10 (13%), and MGMT‐18 (24%) were significantly elevated in patients with glioma. MGMT autoantibody and its protein expression exhibited a significant correlation. The levels of MGMT autoantibodies decreased on the 30th day after operation, reaching preoperative levels, similar to those when tumor recurrence developed. Univariable and multivariable analyses revealed that the only preoperative autoantibodies to MGMT‐02 peptide were independently correlated with recurrence‐free survival. Preoperative seropositive patients were more likely than seronegative patients to have shorter recurrence times and to be resistant to chemoradiotherapy or chemotherapy with temozolomide. Conclusion Monitoring the levels of preoperative serum autoantibodies to MGMT‐02 peptide was useful for predicting patients at high risk of recurrence and treatment response.

Keywords