Coupling of serum CK20 and hyper-methylated CLIP4 as promising biomarker for colorectal cancer diagnosis: from bioinformatics screening to clinical validation.
机构：[1]Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.内科片消化内科云南省第一人民医院[2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.云南省第一人民医院[3]Department of Gastroenterology, The Third People's Hospital of Yunnan Province, Kunming, China.
Colorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of minimally invasive and precise biomarkers is an urgent need for the early diagnosis of CRC. Through bioinformatics analysis of 395 CRC tissues and 63 CRC cell lines, CK18, CK20, de-methylated HPDL and hyper-methylated CLIP4 were identified as candidate serum biomarkers. Then, a training cohort consisting of 60 CRC, 30 colorectal adenomas (CA) and 33 healthy controls and a validation cohort consisting of 60 CRC, 30 CA and 30 healthy controls were enrolled. In the training cohort, enzyme-linked immunosorbent assay (ELISA) showed that CK18 and CK20 were all significantly higher in CRC and CA. CK18 diagnosed CRC with 46.67% sensitivity and 87.3% specificity; CK20 diagnosed CRC with 28.33% sensitivity and 90.47% specificity. Methylation-specific PCR (MSP) indicated that de-methylated HPDL and hyper-methylated CLIP4 were significantly detected in CRC and CA. De-methylated HPDL diagnosed CRC with 36.67% sensitivity and 93.65% specificity and hyper-methylated CLIP4 with 73.33% sensitivity and 84.13% specificity. Random combined analysis suggested that CK20/hyper-methylated CLIP4 diagnosed CRC with 91.67% sensitivity and 82.54% specificity. In the validation cohort, CK20 diagnosed CRC with 36.7% sensitivity and 88.3% specificity and hyper-methylated CLIP4 with 80% sensitivity and 85% specificity. CK20/hyper-methylated CLIP4 diagnosed CRC with 95% sensitivity and 81.7% specificity. Compared with serum biomarkers reported before, CK20/hyper-methylated CLIP4 possessed the potential to be a new effective and precise diagnostic biomarker for CRC.
基金：
2019LCZXKF-XH13, 2020LCZXKF-XH01 and
2021LCZXXF-XH01 from Yunnan Digestive
Endoscopy Clinical Medical Center Foundation
[2X2019-01-02] for Health Commission of Yunnan Province; KHBSH-2020-001 from Post-doctor
Foundation of The First People’s Hospital of Yunnan
Province; 2019FE001(-173) from Yunnan Provincial
Foundation of Science and Technology Department and
Kunming Medical University; 2018NS0264 from
Yunnan Institute of Gastroenterology; 2018FF001(-049)
from Yunnan Provincial Science and Technology
Department; 2017-1-S-16759 from Kunming Science
and Technology Bureau Program
第一作者机构：[1]Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.[2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.[2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
推荐引用方式(GB/T 7714)：
Liu Zhongjian,Tang Hui,Zhang Wen,et al.Coupling of serum CK20 and hyper-methylated CLIP4 as promising biomarker for colorectal cancer diagnosis: from bioinformatics screening to clinical validation.[J].AGING-US.2021,13(24):26161-26179.doi:10.18632/aging.203804.
APA：
Liu Zhongjian,Tang Hui,Zhang Wen,Wang Jinli,Wan Lilan...&Guo Qiang.(2021).Coupling of serum CK20 and hyper-methylated CLIP4 as promising biomarker for colorectal cancer diagnosis: from bioinformatics screening to clinical validation..AGING-US,13,(24)
MLA：
Liu Zhongjian,et al."Coupling of serum CK20 and hyper-methylated CLIP4 as promising biomarker for colorectal cancer diagnosis: from bioinformatics screening to clinical validation.".AGING-US 13..24(2021):26161-26179
