Evidence map›Paper›PMID 41612439›Full record

ArticleCell communication and signaling : CCS2026

Mutation-informed gene pairs to predict melanoma metastasis.

Seongsu Lim, Younggyun Lim, Ju Han Kim

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Seongsu Lim *Seoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-1049-4118
Younggyun Lim *Seoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-4548-4662
Ju Han KimSeoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. juhan@snu.ac.kr.ORCID http://orcid.org/0000-0003-1522-9038

Funding

National Research Foundation of Korea RS-2023-NR077290
6 · The paper itself

Abstract

backgroundMetastasis causes over 90% of cancer-related deaths, including melanoma. However, most anti-cancer treatments focus on reducing tumor size rather than preventing metastatic spread. Therefore, there is a need to identify robust biomarkers that can predict and inhibit metastatic progression without inducing tumor cell death.

methodsWe introduce the novel concept of synthetic anti-metastasis (SAM), which builds on the idea of synthetic lethality (SL). SAM pairs are interactions whose simultaneous impairment suppresses metastasis without inducing cell death. We identified preliminary SAM pairs using somatic mutation and clinical data from The Cancer Genome Atlas (TCGA). We selected the final SAM pairs by excluding previously reported SL interactions and pairs having at least one essential gene from preliminary pairs. We validated these SAM pairs across multiple datasets and tested their clinical relevance using survival analysis and machine learning (ML). Candidate anti-metastatic drugs for melanoma were identified through LINCS-based gene signature analysis, network analysis, and literature review.

resultsWe identified 325 final SAM pairs from 367 preliminary pairs. We found that patients with a high number of co-impairment or -inactivation of SAM pairs showed improved overall survival and reduced metastasis. The ML model based on SAM gene features accurately distinguished primary from metastases melanoma samples (AUROC: 0.940; HR: 0.724), outperforming models built from other known melanoma metastasis-associated genes. Finally, we discovered five compounds - MLN2480, pifithrin-µ, RO4929097, trametinib, and sorafenib - as potential anti-metastatic drugs for melanoma.

conclusionsThis study provides SAM pairs as a novel type of biomarkers that could predict metastatic melanoma prognosis and as therapeutic targets in terms of reducing metastasis risk. Our framework to identify SAM pairs could offer a data-driven strategy to improve the prediction and discover potential treatment for melanoma metastasis through integrated genomic, transcriptomic, and pharmacogenomic analysis.

Indexed as

MelanomaMutationAntineoplastic AgentsHumansMachine LearningNeoplasm MetastasisPyridonesPyrimidinonesSorafenibAntineoplastic AgentsPyridonesPyrimidinonesSorafenibtrametinibDrug repurposingMelanoma metastasisMulti-OmicsPrecision oncology

Identifiers

PMID41612439
PMCPMC12924559

What Socratic holds

Textmetadata
LicenceCC BY
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.