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

Abstract

BACKGROUND:

Early 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.

RESULTS:

Using 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.

CONCLUSIONS:

Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.

• Authors: Jian Zhou, Tong Cheng, Xing Li, Jie Hu, Encheng Li, Ming Ding, Rulong Shen, John P Pineda, Chun Li, Shaohua Lu, Hongyu Yu, Jiayuan Sun, Wenbin Huang, Xiaonan Wang, Han Si, Panying Shi, Jing Liu, Meijia Chang, Maosen Dou, Meng Shi, Xiaofeng Chen, Rex C Yung, Qi Wang, Ning Zhou, Chunxue Bai
• Journal: Clinical epigenetics (Clin Epigenetics) Vol. 13 Issue 1 Pg. 220 (12 14 2021) ISSN: 1868-7083 [Electronic] Germany
• PMID: 34906185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Biomarkers, Tumor

Topics

• Aged
• Biomarkers, Tumor (analysis, genetics)
• DNA Methylation (genetics)
• Early Detection of Cancer (methods, standards, statistics & numerical data)
• Epigenesis, Genetic (genetics)
• Female
• Genomic Imprinting (genetics, physiology)
• Humans
• Lung Neoplasms (diagnosis, genetics)
• Male
• Middle Aged
• Multiple Pulmonary Nodules (etiology, genetics)