A novel Tn antigen epitope-recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Tatsuya Kato; Hideki Ujiie; Kanako C Hatanaka; Ayae Nange; Asami Okumura; Kaho Tsubame; Kentato Naruchi; Masaharu Sato; Kichizo Kaga; Yoshihiro Matsuno; Satoru Wakasa; Yutaka Hatanaka

doi:10.3892/ol.2021.12463

A novel Tn antigen epitope-recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Oncol Lett. 2021 Mar;21(3):202. doi: 10.3892/ol.2021.12463. Epub 2021 Jan 12.

Authors

Affiliations

¹ Department of Cardiovascular and Thoracic Surgery, Hokkaido University Faculty and School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
² Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Hokkaido, 060-8648, Japan.
³ Research Division of Companion Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, 060-8648, Japan.
⁴ Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
⁵ Medicinal Chemistry Pharmaceuticals, Co., Ltd., Sapporo, Hokkaido 060-0009, Japan.
⁶ Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan.

Abstract

Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti-MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope-defined antibody against cancer-associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1-Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1-Tn ED Ab (clone SN-102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN-102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1-Tn expression and epithelial-mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1-Tn expression (MUC1-Tn-H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1-Tn-H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1-Tn-H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of ¹⁸F-fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1-Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1-Tn-H had significantly shorter 5-year overall and disease-free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1-Tn-H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1-Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC.

Keywords: Tn antigen; epithelial-mesenchymal transition; epitope-defined antibody; lung cancer; mucin 1; prognostic factor.