Evidence map›Paper›PMID 42387561›Full record

ArticleCancer cell international2026

From heterogeneity to mechanism: a systems-level analysis pinpoints the S100A8/A9 axis in colorectal cancer.

Hamideh Raeisi, Mahsa Saeedi Niasar, Ehsan Nazemalhosseini Mojarad, Nafiseh Erfanian, Binazir Khanabadi, Samira Saghafi, Hossein Safarpour, Amir Sadeghi

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Article in Cancer cell international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Hamideh RaeisiGastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.ORCID http://orcid.org/0000-0001-8334-4180
Mahsa Saeedi NiasarBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ehsan Nazemalhosseini MojaradGastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nafiseh ErfanianCellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Binazir KhanabadiBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Samira SaghafiStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Hossein SafarpourCellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. safarpour701@yahoo.com.
Amir SadeghiGastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. amirsadeghimd@yahoo.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe functional roles of the S100 protein family in colorectal cancer (CRC) are enigmatic, marked by widespread dysregulation but limited prognostic utility. This heterogeneity obscures their potential as therapeutic targets.

methodsWe employed a multi-omics strategy to deconstruct this complexity, integrating bulk transcriptomics (TCGA), large-scale single-cell RNA-seq atlases, and machine learning-based prioritization. Cell-type-specific expression patterns were contextualized using the spatial annotation of cell origins available within the Pan-GI Cell Atlas. Key findings were validated experimentally via qRT-PCR in a 30-patient cohort and functionally assessed using in vitro assays.

resultsWhile 17 S100 genes were differentially expressed in bulk tumor tissue, they lacked collective prognostic power. Single-cell analysis resolved this paradox, revealing that the expression of key alarmins S100A8 and S100A9 is not tumor-intrinsic but is highly concentrated in tumor-infiltrating myeloid cells. This myeloid-specific signature was associated with high-grade disease and progressively increased from polyps to tumors. We experimentally validated that S100A8 and S100A9 mRNA levels are significantly elevated in CRC tissues versus adjacent normal controls (S100A8, p = 0.004; S100A9, p = 0.012). Functionally, recombinant S100A8 and S100A9 acted as drivers of inflammation, directly inducing a pro-inflammatory cascade including NF-κB, IL-6, and IL-8 in CRC cells.

conclusionsOur findings clarify the S100 family's role in CRC, identifying the myeloid-derived S100A8 and S100A9 axis as a key amplifier of the pro-tumorigenic inflammatory microenvironment. This axis represents a critical nexus between innate immunity and carcinogenesis, offering a promising target for novel anti-inflammatory or immunomodulatory therapies in CRC.

Indexed as

Colorectal cancerMulti-omicsS100A8S100A9S100 proteinsSingle-cell transcriptomics

Identifiers

PMID42387561
PMCPMC13595796

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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.