TY - JOUR
T1 - The prevalence of cancer-associated autoantibodies in patients with gastric cancer and progressive grades of premalignant lesions
AU - Meistere, Irēna
AU - Werner, Simone
AU - Zayakin, Pawel
AU - Siliņa, Karīna
AU - Rulle, Undīne
AU - Pismennaja, Angelina
AU - Šantare, Daiga
AU - Kikuste, Ilze
AU - Isajevs, Sergejs
AU - Leja, Marcis
AU - Kupčinskas, Limas
AU - Kupčinskas, Juozas
AU - Jonaitis, Laimas
AU - Wu, Chun Ying
AU - Brenner, Hermann
AU - Linē, Aija
AU - Kalniņa, Zane
N1 - Publisher Copyright:
©2017 AACR.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Background: Serum autoantibodies against tumor-associated antigens (TAAs) are detectable in early-stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure. Methods: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia. Results: Six antigens, including CTAG1B/CTAG2, DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly reacting with sera from gastric cancer patients when compared with healthy controls, and the seroreactivity was associated with intestinal-type gastric cancer, but not with patients' Helicobacter pylori status, grade, age, gender, or stage of gastric cancer. We detected gastric cancer–associated seroreactivity in 13% of patients with advanced/severe intestinal metaplasia, which was increased in comparison with mild/moderate intestinal metaplasia (5.3%) and was comparable with that seen in early-stage gastric cancer patients (12%). Moreover, by testing serum samples taken 1 to 9 years before the clinical diagnosis of 18 incident gastric cancer cases, we detected autoantibody responses against several TAAs—SOX2, MYC, BIRC5, IGF2BP1, and MUC1. Conclusions: Our results suggest that humoral immune response against TAAs is generated already during premalignant stages. Impact: Based on the obtained results, cancer-associated autoantibodies might make a valuable contribution to the stratification of high-risk patients with premalignant lesions in the stomach through enhancing the positive predictive power of existing risk models.
AB - Background: Serum autoantibodies against tumor-associated antigens (TAAs) are detectable in early-stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure. Methods: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia. Results: Six antigens, including CTAG1B/CTAG2, DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly reacting with sera from gastric cancer patients when compared with healthy controls, and the seroreactivity was associated with intestinal-type gastric cancer, but not with patients' Helicobacter pylori status, grade, age, gender, or stage of gastric cancer. We detected gastric cancer–associated seroreactivity in 13% of patients with advanced/severe intestinal metaplasia, which was increased in comparison with mild/moderate intestinal metaplasia (5.3%) and was comparable with that seen in early-stage gastric cancer patients (12%). Moreover, by testing serum samples taken 1 to 9 years before the clinical diagnosis of 18 incident gastric cancer cases, we detected autoantibody responses against several TAAs—SOX2, MYC, BIRC5, IGF2BP1, and MUC1. Conclusions: Our results suggest that humoral immune response against TAAs is generated already during premalignant stages. Impact: Based on the obtained results, cancer-associated autoantibodies might make a valuable contribution to the stratification of high-risk patients with premalignant lesions in the stomach through enhancing the positive predictive power of existing risk models.
UR - http://www.scopus.com/inward/record.url?scp=85031671738&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-17-0238
DO - 10.1158/1055-9965.EPI-17-0238
M3 - Article
C2 - 28768706
AN - SCOPUS:85031671738
SN - 1055-9965
VL - 26
SP - 1564
EP - 1574
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 10
ER -