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Early detection of colorectal cancer based on circular dna and common clinical detection indicators

World Journal of Gastrointestinal Surgery 2022年第8期14卷 833-848页

作者： Jian Li Tao Jiang Zeng-Ci Ren Zhen-Lei Wang Peng-Jun Zhang Guo-An Xiang The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of General Surgery Guangdong Second Provincial General HospitalGuangzhou 510317Guangdong ProvinceChina Department of General Surgery Henan Tumor HospitalAffiliated Tumor Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina Medicine Innovation Research Division of Chinese PLA General Hospital Beijing 100853China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Interventional Therapy DepartmentPeking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Colorectal cancer(CRC) is the third most common cancer worldwide, and it is the second leading cause of death from cancer in the world, accounting for approximately 9% of all cancer deaths. Early detection of CRC is urgently needed in clinical *** To build a multi-parameter diagnostic model for early detection of *** Total 59 colorectal polyps(CRP) groups, and 101 CRC patients(38 early-stage CRC and 63 advanced CRC) for model establishment. In addition, 30 CRP groups,and 62 CRC patients(30 early-stage CRC and 32 advanced CRC) were separately included to validate the model. 51 commonly used clinical detection indicators and the 4 extrachromosomal circular dna markers NDUFB7, CAMK1D, PIK3CD and PSEN2 that we screened earlier. Four multi-parameter joint analysis methods:binary logistic regression analysis, discriminant analysis, classification tree and neural network to establish a multi-parameter joint diagnosis *** Neural network included carcinoembryonic antigen(CEA), ischemia-modified albumin(IMA),sialic acid(SA), PIK3CD and lipoprotein a(LPa) was chosen as the optimal multi-parameter combined auxiliary diagnosis model to distinguish CRP and CRC group, when it differentiated 59CRP and 101 CRC, its overall accuracy was 90.8%, its area under the curve(AUC) was 0.959(0.934,0.985), and the sensitivity and specificity were 91.5% and 82.2%, respectively. After validation,when distinguishing based on 30 CRP and 62 CRC patients, the AUC was 0.965(0.930-1.000), and its sensitivity and specificity were 66.1% and 70.0%. When distinguishing based on 30 CRP and 32early-stage CRC patients, the AUC was 0.960(0.916-1.000), with a sensitivity and specificity of 87.5% and 90.0%, distinguishing based on 30 CRP and 30 advanced CRC patients, the AUC was 0.970(0.936-1.000), with a sensitivity and specificity of 96.7% and 86.7%.CONCLUSION We built a multi-parameter neural network diagnostic model included CEA, IMA, SA, PIK3CD and LPa for early detect

关键词： Colorectal cancer Colorectal polyps Multi-parameter circular dna Neural network

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dna sequences homologous to hepatitis C virus(HCV) in the extrachromosomal circular dna in peripheral blood mononuclear cells of HCV-negative subjects

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第8期20卷 637-646页

作者： Reinhard H. Dennin Jian-Er Wo Formerly Department of Infectious Diseases and Microbiology University of Lübeck University Hospital Schleswig-Holstein 23538 Lübeck Germany State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Institute of Infectious Diseases the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

Objective: This study aimed to investigate dna sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These dna sequences are present in the whole dna extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5'-noncoding region (5'-NCR) homologous dna sequences could be contained in the extrachromosomal circular dna (eccdna) fraction as part of the whole cellular dna. Methods: Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccdna, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed. Results: The PCR tests revealed dna sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5'-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5'-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the dna sequences of the 5'-NCR revealed a broad diversity of individual patterns of methylation. Conclusions: The experimental results confirm our assumption that parts of the HCV 5'-NCR genomic RNA sequences are present at the dna level in the eccdna fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.

关键词： Hepatitis C virus (HCV) 5'-Non-coding region (5'-NCR) Human genome Extrachromosomal dna circular dna Pattern of methylation

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