Evidence map›Paper›PMID 40038757›Full record

ArticleJournal of translational medicine2025

Molecular subtyping of stage I lung adenocarcinoma via molecular alterations in pre-invasive lesion progression.

Jun Shang, He Jiang, Yue Zhao, Jingcheng Yang, Yicong Lin, Naixin Zhang, Luyao Ren, Qingwang Chen, Ying Yu, Leming Shi and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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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

13 authors.

Jun Shang *Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
He Jiang *State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Yue Zhao *Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
Jingcheng YangState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Yicong LinDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Naixin ZhangState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Luyao RenState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Qingwang ChenState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Ying YuState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Leming ShiState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China. lemingshi@fudan.edu.cn.
Yuan LiDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. lumoxuan2009@163.com.
Haiquan ChenDepartments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China. hqchen1@yahoo.com.
Yuanting ZhengState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China. zhengyuanting@fudan.edu.cn.

Funding

State Sponsored Postdoctoral Fellowship Programme GZC20230501
6 · The paper itself

Abstract

backgroundPatients with adenocarcinoma in situ (AIS) and minimally invasive (MIA) lung adenocarcinoma (LUAD) are curable by surgery, whereas 20% stage I patients die within five years after surgery. We hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. Therefore, we tried to reveal molecularly and prognostically distinct subtypes of stage I LUAD by applying key molecular alterations from AIS/MIA to invasive LUAD progression.

methodsThe RNA and whole-exome sequencing data of 197 tumor-normal matched samples from patients with AIS, MIA, and invasive LUAD were analyzed. ddPCR quantified 202 samples from 182 patients at the absolute expression level. Immunohistochemical quantified the protein expression levels of ACTA2. RNA-seq data from 954 LUAD patients, including 541 stage I patients, along with 12 published datasets comprising 1,331 stage I LUAD patients, were used to validate our findings.

resultsFocal adhesion (FA) was identified as the only pathway significantly perturbed at both genomic and transcriptomic levels by comparing 98 AIS/MIA and 99 LUAD. Then, two FA genes (COL11A1 and THBS2) were found strongly upregulated from AIS/MIA to stage I while steadily expressed from normal to AIS/MIA. Furthermore, unsupervised clustering separated stage I patients into two molecularly and prognostically distinct subtypes (S1 and S2) based on COL11A1 and THBS2 expressions (FA2). Subtype S1 resembled AIS/MIA, whereas S2 exhibited more somatic alterations and activated cancer-associated fibroblast. Immunohistochemistry on 73 samples also observed that CAF was more active in S2 compared to S1 and AIS/MIA. The prognostic value of these two genes identified from our knowledge-driven process was confirmed by 541 stage I patients in a prospective dataset, ddPCR and 12 published datasets.

conclusionsWe successfully revealed two molecularly and prognostically distinct subtypes of stage I LUAD by applying key molecular alterations from AIS/MIA to invasive LUAD progression. Our model may help reliably identify high-risk stage I patients for more intensive post-surgery treatment.

Indexed as

Adenocarcinoma of LungDisease ProgressionLung NeoplasmsAgedFemaleFocal AdhesionsGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm InvasivenessNeoplasm StagingReproducibility of ResultsCOL11A1Lung adenocarcinomaMolecular subtypesOverfitting-resistantPre/minimally invasivePrognosisTHBS2Unsupervised clustering

Identifiers

PMID40038757
PMCPMC11877874

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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.