Evidence mapPaperPMID 41845530Full record

ArticleGenome medicine2026

Multi-omics reveals key molecular and cellular features of advanced small cell lung cancers associated with distinct therapeutic opportunities.

Katia Nones, Vanessa Lakis, Andrew J Dalley, Kimberley Ryan, Haarika Chittoory, Kaltin Ferguson, Kate Fitzgerald, Felicity Newell, Lambros T Koufariotis, Farzad Bashirzadeh and 27 more

Abstract read
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

37 authors.

Katia Nones *Faculty of Health, Medicine and Behavioural Sciences, Medical School, The University of Queensland, Brisbane, QLD, 4102, Australia. k.nones@uq.edu.au.
Vanessa Lakis *Faculty of Health, Medicine and Behavioural Sciences, Medical School, The University of Queensland, Brisbane, QLD, 4102, Australia.
Andrew J DalleyFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Kimberley RyanDepartment of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, QLD, 4029, Australia.
Haarika ChittooryFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Kaltin FergusonFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Kate FitzgeraldFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Felicity NewellCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
Lambros T KoufariotisCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
Farzad BashirzadehDepartment of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, QLD, 4029, Australia.
Jung Hwa SonDepartment of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, QLD, 4029, Australia.
Mahendra SinghPathology Queensland, The Royal Brisbane & Women's Hospital, Brisbane, 4029, Australia.
Lakshmy NandakumarPathology Queensland, The Royal Brisbane & Women's Hospital, Brisbane, 4029, Australia.
David FairbairnPathology Queensland, The Royal Brisbane & Women's Hospital, Brisbane, 4029, Australia.
Margaret CummingsFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Daniel SteinfortDepartment of Respiratory and Sleep Thoracic Medicine, Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
Jemma J ChristieDepartment of Respiratory and Sleep Thoracic Medicine, Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
Matthew GibneyDepartment of Respiratory and Sleep Thoracic Medicine, Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
Jonathan P WilliamsonDepartment of Thoracic Medicine, Liverpool Hospital Sydney, Sydney, NSW, 2170, Australia.
Andrew PattisonDepartment of Respiratory and Sleep Medicine, Sunshine Coast University Hospital, Birtinya, QLD, 4575, Australia.
Louise McIntoshDepartment of Respiratory and Sleep Medicine, Sunshine Coast University Hospital, Birtinya, QLD, 4575, Australia.
Carl PahoffDepartment of Respiratory Medicine, Gold Coast University Hospital, Southport, QLD, 4215, Australia.
Phan Tien NguyenDepartment of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
Jelena SolujicDepartment of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
Michael BrownDepartment of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
Scott TwaddellDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, 2305, Australia.
David ArnoldDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, 2305, Australia.
Christopher GraingeDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, 2305, Australia.
Shailendra GuneNSW Health Pathology South, Liverpool Hospital, Sydney, Sydney, NSW, 2170, Australia.
Oliver HolmesCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
Conrad LeonardCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
Scott WoodCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
John V PearsonCancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
Sunil R LakhaniFaculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Peter T Simpson *Faculty of Health, Medicine and Behavioural Sciences, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4006, Australia.
Nicola Waddell *Cancer Program, QIMR Berghofer, Brisbane, QLD, 4006, Australia.
David Fielding *Faculty of Health, Medicine and Behavioural Sciences, Medical School, The University of Queensland, Brisbane, QLD, 4102, Australia.

Funding

Cancer Australia 1147067Cancer Council Queensland 1147067Cancer Council Queensland AACR 000000027Medical Research Futures Fund Genomics Health Futures Mission 2009160
6 · The paper itself

Abstract

backgroundSmall cell lung cancer (SCLC) is an aggressive disease that is often diagnosed at an advanced stage when surgery is no longer feasible. The lack of tumor tissue and rapid clinical decline of patients have hindered the feasibility of large omics studies. However, with advances in omics technologies recent studies have started to unravel the molecular heterogeneity of SCLCs.

methodsHere, 82 fresh EBUS-TBNA aspirates underwent methylation profiling (EPIC arrays), with subsets of those subjected to whole-genome sequencing (n = 76), RNA-seq (n = 48) and blood cfDNA sequencing (n = 69) to characterize the molecular features of SCLCs.

resultsMethylation profiling revealed four sub-groups associated with distinct survival and extrinsic/intrinsic tumor features. Groups 1 and 2 presented increased expression of ASCL1. Group 1 tumors had a greater proportion of CD8 + T cells (immune enriched-NE) and patients with better survival. Group 2 (SCLC-A) harbored the largest number of cases, and high expression of SLFN11 and DLL3, as potential therapeutic options. Group 3 tumors presented increased expression and hypomethylation of NEUROD1 (SCLC-N), with a greater proportion of fibroblasts. Group 4 tumors expressed POU2F3 and/or YAP1, had increased expression of non-neuroendocrine genes (non-NE) and had the worst survival. TACSTD2 expression was higher in Group 4, suggesting a potential therapeutic option for this group. SEZ6, another potential therapeutic option, was highly expressed in most SCLCs. These results highlight that novel therapeutic options may need to be considered in the context of SCLC heterogeneity.

conclusionsWe showed that methylation of the most common source of tumor tissue in the clinical setting can stratify SCLCs with distinct clinical outcomes and potentially tailored therapeutic options. Methylation can characterize the intrinsic and extrinsic heterogeneity of SCLCs and fuel the discovery of novel therapeutic vulnerabilities to help bridge the gap between research and clinical application to improve care for SCLC patients.

Indexed as

Lung NeoplasmsSmall Cell Lung CarcinomaAgedBasic Helix-Loop-Helix ProteinsBiomarkers, TumorDNA MethylationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiddle AgedMultiomicsASCL1 protein, humanBasic Helix-Loop-Helix ProteinsBiomarkers, TumorDLL3 protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsCfDNADNA methylationMulti-omicsPrecision oncologySmall cell lung cancerTranscriptomicsTumor heterogeneityWhole-genome sequencing

Identifiers

PMID41845530
PMCPMC13107910

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.