Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection

Zhibin Chen; Jie Xing; Cuiling Zheng; Qianyu Zhu; Pingping He; Donghu Zhou; Xiaojin Li; Yanmeng Li; Saiping Qi; Qin Ouyang; Bei Zhang; Yibin Xie; Jiansong Ren; Bangwei Cao; Shengtao Zhu; Jian Huang

doi:10.3389/fonc.2023.1161489

Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection

Front Oncol. 2023 May 12:13:1161489. doi: 10.3389/fonc.2023.1161489. eCollection 2023.

Authors

Zhibin Chen¹, Jie Xing², Cuiling Zheng³, Qianyu Zhu¹, Pingping He¹, Donghu Zhou¹, Xiaojin Li¹, Yanmeng Li¹, Saiping Qi¹, Qin Ouyang¹, Bei Zhang¹, Yibin Xie⁴, Jiansong Ren⁵, Bangwei Cao⁶, Shengtao Zhu², Jian Huang^{1

7}

Affiliations

¹ Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
² Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
³ Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁶ Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
⁷ National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Abstract

Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC.

Methods: We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance.

Results: The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression.

Conclusions: Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

Keywords: autoantibody; early detection; esophageal squamous cell carcinoma; high-grade intraepithelial neoplasia; serum biomarker.

Grants and funding

This work was funded by grants from National Major Science and Technology Projects of China (No.2017ZX10201201), and the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXZ01).