Evidence map›Paper›PMID 35073982›Full record

ArticleClinical epigenetics2022

Integrated 5-hydroxymethylcytosine and fragmentation signatures as enhanced biomarkers in lung cancer.

Xinlei Hu, Kai Luo, Hui Shi, Xiaoqin Yan, Ruichen Huang, Bi Zhao, Jun Zhang, Dan Xie, Wei Zhang

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07126626 (Multi-center Prospective Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer), which is not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07126626 not yet recruitingnot on this mapstarted 2025, after this paper: background citation

Multi-center Prospective Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer

TypeobservationalSponsorGene SolutionsRan2025 to 2027Enrolled1,184ConditionsLung Diseases, Lung Cancer Screening
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 36 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Xinlei Hu *National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China.
Kai Luo *National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China.
Hui Shi *Department of Respiratory and Critical Care Medicine, First Affiliated Hospital The Second Military Medical University, Shanghai, 200433, Shanghai, People's Republic of China.
Xiaoqin Yan *Tailai Inc., Shanghai, 200233, People's Republic of China.
Ruichen HuangDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital The Second Military Medical University, Shanghai, 200433, Shanghai, People's Republic of China.
Bi ZhaoDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital The Second Military Medical University, Shanghai, 200433, Shanghai, People's Republic of China.
Jun ZhangNational Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China.
Dan XieNational Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China. danxie@scu.edu.cn.ORCID 0000-0001-5388-5541
Wei ZhangDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital The Second Military Medical University, Shanghai, 200433, Shanghai, People's Republic of China. zhangweismmu@126.com.
Second Military Medical University · CNSichuan University · CN

Funding

Clinical Research Incubation Project of Sichuan University West China Hospital 2020HXFH006Department of Science and Technology of Sichuan Province 2020YFS0051Scientific Research Project by Shanghai Science and Technology Committee 19411950400
6 · The paper itself

Abstract

backgroundLung cancer is one of most common cancers worldwide, with a 5-year survival rate of less than 20%, which is mainly due to late-stage diagnosis. Noninvasive methods using 5-hydroxymethylation of cytosine (5hmC) modifications and fragmentation profiles from 5hmC cell-free DNA (cfDNA) sequencing provide an opportunity for lung cancer detection and management.

resultsA total of 157 lung cancer patients were recruited to generate the largest lung cancer cfDNA 5hmC dataset, which mainly consisted of 62 lung adenocarcinoma (LUAD), 48 lung squamous cell carcinoma (LUSC) and 25 small cell lung cancer (SCLC) patients, with most patients (131, 83.44%) at advanced tumor stages. A 37-feature 5hmC model was constructed and validated to distinguish lung cancer patients from healthy controls, with areas under the curve (AUCs) of 0.8938 and 0.8476 (sensitivity = 87.50% and 72.73%, specificity = 83.87% and 80.60%) in two distinct validation sets. Furthermore, fragment profiles of cfDNA 5hmC datasets were first explored to develop a 48-feature fragmentation model with good performance (AUC = 0.9257 and 0.822, sensitivity = 87.50% and 78.79%, specificity = 80.65% and 76.12%) in the two validation sets. Another diagnostic model integrating 5hmC signals and fragment profiles improved AUC to 0.9432 and 0.8639 (sensitivity = 87.50% and 83.33%, specificity = 90.30% and 77.61%) in the two validation sets, better than models based on either of them alone and performing well in different stages and lung cancer subtypes. Several 5hmC markers were found to be associated with overall survival (OS) and disease-free survival (DFS) based on gene expression data from The Cancer Genome Atlas (TCGA).

conclusionsBoth the 5hmC signal and fragmentation profiles in 5hmC cfDNA data are sensitive and effective in lung cancer detection and could be incorporated into the diagnostic model to achieve good performance, promoting research focused on clinical diagnostic models based on cfDNA 5hmC data.

Indexed as

5-MethylcytosineAdultAgedAged, 80 and overBiomarkers, TumorChinaDNA FragmentationDNA MethylationFemaleHumansLung NeoplasmsMaleMiddle Aged5-hydroxymethylcytosine5-MethylcytosineBiomarkers, TumorCancer diagnosisCell-free 5hmC sequencingCell-free DNA fragmentationLiquid biopsyLung cancer

Identifiers

PMID35073982
PMCPMC8787948
OpenAlexW4206932164

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.