ANO1 protein as a potential biomarker for esophageal cancer prognosis and precancerous lesion development prediction
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Li Shang1,*, Jia-Jie Hao1,*, Xue-Ke Zhao3,*, Jian-Zhong He4,*, Zhi-Zhou Shi1, Hui-Juan Liu5, Li-Fei Wu6, Yan-Yi Jiang1, Feng Shi1, Hai Yang1, Yu Zhang1, Yi-Zhen Liu1, Tong-Tong Zhang1, Xin Xu1, Yan Cai1, Xue-Mei Jia5, Min Li6, Qi-Min Zhan1, En-Min Li4, Li-Dong Wang3, Wen-Qiang Wei2, Ming-Rong Wang1
1State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
2Department of Cancer Epidemiology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
3Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450000, China
4Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
5Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China
6Department of Gastroenterology, Anqing City Hospital, Affiliated Anqing Hospital of Anhui Medical University, Anqing 246003, China
*These authors have contributed equally to this work
Ming-Rong Wang, e-mail: firstname.lastname@example.org
Wen-Qiang Wei, e-mail: email@example.com
Li-Dong Wang, e-mail: firstname.lastname@example.org
En-Min Li, e-mail: email@example.com
Keywords: ANO1, esophageal squamous cell carcinoma, precancerous lesions, biomarker, prognosis
Received: September 17, 2015 Accepted: March 01, 2016 Published: March 21, 2016
Objectives: Anoctamin 1 (ANO1) has been found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous study. Herein we showed the clinical relevance of ANO1 alterations with ESCC and esophageal precancerous lesion progression.
Results: ANO1 was detected in 38.1% (109/286) and 25.4% (77/303) of tumors in the two cohorts, but in none of morphologically normal operative margin tissues. ANO1 expression was significantly associated with a shorter overall survival (OS), especially in patients with moderately differentiated and stage IIA tumors. In 499 iodine-unstained biopsies from the endoscopic screening cohort in 2005-2007, all the 72 pathologically normal epithelial mucosa presented negative immunostaining, whereas ANO1 expression was observed in 3/11 tumors and 5/231 intraepithelial lesions. 7/8 ANO1-positive cases had developed unfavorable outcomes revealed by endoscopic follow-up in 2012. Analysis of another independent cohort of 148 intraepithelial lesions further confirmed the correlation between ANO1 expression and progression of precancerous lesions. 3/4 intraepithelial lesions with ANO1 expression had developed ESCC within 4-9 years after the initial endoscopic examination.
Methods: Immunohistochemistry (IHC) was performed to examine ANO1 expression in surgical ESCC specimens and two independent cohorts of esophageal biopsies from endoscopic screening in high-incidence area of ESCC in northern China. Association between ANO1 expression, clinico-pathologic parameters, and the impact on overall survival was analyzed.
Conclusions: Positive ANO1 is a promising biomarker to predict the unfavorable outcome for ESCC patients. More importantly, it can predict disease progression of precancerous lesions.
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