Evidence map›Paper›PMID 41912434›Full record

ArticleThe oncologist2026

Degrees of H2AX phosphorylation correlate with unique features of the intratumoral immune microenvironment in colorectal carcinomas.

Enrico Berrino, Sara Erika Bellomo, Maria Costanza Aquilano, Marta Falcinelli, Anita Chesta, Emanuele Valtorta, Daniela Zampieri, Gianluca Mauri, Giuseppe Sala, Silvia Marsoni and 7 more

Abstract read
In one paragraph

Article in The oncologist, 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

17 authors.

Enrico BerrinoPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.ORCID 0000-0001-6728-5619
Sara Erika BellomoPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.
Maria Costanza AquilanoDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Marta FalcinelliIFOM ETS-The AIRC Institute of Molecular Oncology, Milan 20139, Italy.
Anita ChestaPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.ORCID 0000-0001-9770-5282
Emanuele ValtortaDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Daniela ZampieriPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.
Gianluca MauriDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Giuseppe SalaDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Silvia MarsoniIFOM ETS-The AIRC Institute of Molecular Oncology, Milan 20139, Italy.ORCID 0000-0002-5361-7122
Alberto BardelliIFOM ETS-The AIRC Institute of Molecular Oncology, Milan 20139, Italy.
Andrea Sartore-BianchiDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Salvatore SienaDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Anna SapinoPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.
Emanuela BonoldiDepartment of Hematology, Oncology, and Molecular Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, 20162 Italy.
Fabrizio d'Adda di FagagnaIFOM ETS-The AIRC Institute of Molecular Oncology, Milan 20139, Italy.
Caterina MarchiòPathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, 10060 Italy.

Funding

AriSLA DDR&ALS FG_24_2020CARESSERC TELORNAGING-835103ERC POC TELOVACCINE 101113229ERC POC TELOVACCINE AIRC-IG 21762ERC POC TELOVACCINE AIRC-IG 30471ERC POC TELOVACCINE GMR23T2007European Research Council (ERC)European UnionEuropean Union or the European Research CouncilEuropean Union's Horizon 2020 101007937European Union's Horizon 2020 101020342FONDAZIONE AIRC 21091Fondazione Oncologia Niguarda ETSFondazione Piemontese per la Ricerca sul Cancro-ONLUSFondo Divisionale Oncologia FalckGrande Ospedale Metroplitano NiguardaItalian Ministry of Health Ricerca Corrente 2024-2025Next Generation EUPERSIST-SEQ 289ASSO22POR FESR InterSLA DSB.AD004.294Progetti di Ricerca di Interesse Nazionale (PRIN) 2020CXFL4TProgetti di Ricerca di Interesse Nazionale (PRIN) 2022R7LH5T
6 · The paper itself

Abstract

backgroundThe phosphorylated form of the histone H2AX (γH2AX), a sensor of DNA double-strand breaks (DSB), can serve as a biomarker of DNA damage and therapy response. This study aimed to evaluate the association between γH2AX expression and pathological, molecular, and immune features in colorectal cancer (CRC). PATIENTS AND

methodsLevels of γH2AX were assessed by immunohistochemistry in a cohort of 198 CRCs, alongside immune-related markers (CD3 and CD8). A sub-cohort of 65 CRCs (26 γH2AX- and 39 γH2AX+) underwent RNA extraction and gene expression profiling using the IO360 Nanostring Panel to infer immune cell composition. Overall survival data were analyzed for exploratory correlations.

resultsγH2AX+ CRCs (155/198, 78%) were significantly associated with higher stage and tumor grade (P < .01). A lower γH2AX prevalence was found in MMR-deficient tumors (64%) compared to MMR-proficient cases (81%, P = .05). γH2AX+ tumors showed increased CD3+ cell infiltration in the overall population (P = .038) and in MMR-proficient CRCs (P = .028). Gene expression analysis revealed higher T-cell counts (P < .01) and reduced B-cell abundance (P < .01) in γH2AX+ CRCs. Unsupervised clustering identified 3 immune subgroups with differential γH2AX accumulation. Cluster #3, enriched in γH2AX+ tumors, displayed increased CD8+ T-cells and conferred the best survival outcome.

conclusionElevated γH2AX expression correlates with MMR proficiency, aggressive histopathologic features, and a distinctive immune-active microenvironment in CRC. These findings may support γH2AX as a marker of immune-modulated CRC subgroups with potential prognostic and therapeutic relevance.

Indexed as

Colorectal NeoplasmsHistonesTumor MicroenvironmentAgedBiomarkers, TumorFemaleHumansMaleMiddle AgedPhosphorylationPrognosisBiomarkers, TumorH2AX protein, humanHistonescolorectal cancerimmune infiltrationMMR deficientlyMMR proficiencyyH2Ax

Identifiers

PMID41912434
PMCPMC13071407

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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.