Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules

Clinical Epigenetics

Meng Shi¹  Xiaofeng Chen¹  Rex C. Yung²  Hongyu Yu³  Wenbin Huang⁴  Rulong Shen⁵  Jing Liu⁶  Chun Li⁷  Maosen Dou⁷  Shaohua Lu⁷  Meijia Chang⁷  Jie Hu⁷  Chunxue Bai⁸  Jian Zhou⁸  Jiayuan Sun⁹  Ming Ding^1,10  Qi Wang^1,11  Encheng Li^1,11  Tong Cheng^1,12  Panying Shi^1,12  John P. Pineda^1,12  Xing Li^1,12  Ning Zhou^1,12  Xiaonan Wang^1,12  Han Si^1,12 

[1] Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, 200040, Shanghai, China;Department of Oncology, Johns Hopkins University School of Medicine, 21207, Baltimore, MD, USA;Department of Pathology, Changzheng Hospital, Navy Medical University, 200003, Shanghai, China;Department of Pathology, Nanjing First Hospital, 210006, Nanjing, Jiangsu, China;Department of Pathology, Ohio State University Wexner Medical Center, 43210, Columbus, OH, USA;Department of Pathology, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, 264000, Yantai, Shandong, China;Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China;Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China;Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 200032, Shanghai, China;Department of Respiratory Endoscopy and Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, China;Department of Respiratory Medicine, The Affiliated Zhongda Hospital of Southeast University, 210009, Nanjing, Jiangsu, China;Department of Respiratory Medicine, The Second Hospital Affiliated to Dalian Medical University, 116044, Dalian, Liaoning, China;Epigenetics Lab, Chinese Alliance Against Lung Cancer, 6th Floor, Building 5, No.66, Jinghuidongdao Road, 214135, Wuxi, Jiangsu, China;

关键词: Epigenetics;    Genomic imprinting;    Cancer biomarkers;    In situ hybridization;    Lung cancer early diagnosis;    Pulmonary nodules;   

DOI  :  10.1186/s13148-021-01203-5

来源: Springer

【 摘 要 】

BackgroundEarly lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions.ResultsUsing the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm.ConclusionsOur findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.

【 授权许可】

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