Novel visualized quantitative epigenetic imprinted gene biomarkers diagnose the malignancy of ten cancer types

Autor: Rex Yung, Hongxun Wu, Panying Shi, Chuanliang Xu, Rulong Shen, Xiaonan Wang, Pengcheng Zhao, Wenbo Bu, Yun Zhu, Han Si, Chun-Lin Lin, Ning Zhou, Xing Li, Huixiong Xu, John Pineda, Jian Zhou, Hongyu Yu, Chunxue Bai, Shaohua Lu, Jiandong Bao, Yun Liu, Tong Cheng, Yongjie Deng, Shuxiong Zeng
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Genomic imprinting
GRB10 Adaptor Protein
Locus (genetics)
Computational biology
Biology
medicine.disease_cause
Sensitivity and Specificity
Multiallelic expression
03 medical and health sciences
0302 clinical medicine
Biallelic expression
GTP-Binding Proteins
Neoplasms
Biomarkers
Tumor
Chromogranins
GTP-Binding Protein alpha Subunits
Gs
Genetics
medicine
GNAS complex locus
Humans
Epigenetics
Allele
Molecular Biology
Alleles
Early Detection of Cancer
In Situ Hybridization
Genetics (clinical)
Cancer biomarker
Gene Expression Profiling
Carcinoma in situ
Methodology
Ribonucleoproteins
Small Nuclear
Small nuclear ribonucleoprotein polypeptide N
medicine.disease
Gene Expression Regulation
Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Female
Carcinogenesis
Algorithms
Developmental Biology
Zdroj: Clinical Epigenetics
ISSN: 1868-7083
1868-7075
Popis: Background Epigenetic alterations are involved in most cancers, but its application in cancer diagnosis is still limited. More practical and intuitive methods to detect the aberrant expressions from clinical samples using highly sensitive biomarkers are needed. In this study, we developed a novel approach in identifying, visualizing, and quantifying the biallelic and multiallelic expressions of an imprinted gene panel associated with cancer status. We evaluated the normal and aberrant expressions measured using the imprinted gene panel to formulate diagnostic models which could accurately distinguish the imprinting differences of normal and benign cases from cancerous tissues for each of the ten cancer types. Results The Quantitative Chromogenic Imprinted Gene In Situ Hybridization (QCIGISH) method developed from a 1013-case study which provides a visual and quantitative analysis of non-coding RNA allelic expressions identified the guanine nucleotide-binding protein, alpha-stimulating complex locus (GNAS), growth factor receptor-bound protein (GRB10), and small nuclear ribonucleoprotein polypeptide N (SNRPN) out of five tested imprinted genes as efficient epigenetic biomarkers for the early-stage detection of ten cancer types. A binary algorithm developed for cancer diagnosis showed that elevated biallelic expression (BAE), multiallelic expression (MAE), and total expression (TE) measurements for the imprinted gene panel were associated with cell carcinogenesis, with the formulated diagnostic models achieving consistently high sensitivities (91–98%) and specificities (86–98%) across the different cancer types. Conclusions The QCIGISH method provides an innovative way to visually assess and quantitatively analyze individual cells for cancer potential extending from hyperplasia and dysplasia until carcinoma in situ and invasion, which effectively supplements standard clinical cytologic and histopathologic diagnosis for early cancer detection. In addition, the diagnostic models developed from the BAE, MAE, and TE measurements of the imprinted gene panel GNAS, GRB10, and SNRPN could provide important predictive information which are useful in early-stage cancer detection and personalized cancer management.
Databáze: OpenAIRE
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