Evidence map›Paper›PMID 41965872›Full record

ReviewSystematic reviews2026

Immune and stromal signaling networks in chordoma: an evidence-weighted review of ligand-receptor interactions and therapeutic implications.

Panpan Hu, Juncai Lei, Suiyong Du, Shengxin Zeng, Peilin Hua, Hua Zhou, Feng Wei

Abstract readReview
In one paragraph

Review in Systematic reviews, 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

7 authors.

Panpan Hu *Department of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China. pphu@bjmu.edu.cn.
Juncai Lei *Department of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.
Suiyong Du *Department of Spine Surgery, Norinco General Hospital, Zhangba Road, Xi'an, Shanxi, 710065, China.
Shengxin ZengDepartment of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.
Peilin HuaDepartment of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.
Hua ZhouDepartment of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.
Feng WeiDepartment of Orthopaedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China. weifeng@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThis scoping review aimed to systematically map reported ligand-receptor (L-R) interactions in chordoma, classify the strength of supporting evidence, and integrate mechanistic, spatial, and clinical findings to inform translational prioritization.

methodsA systematic search of PubMed, Embase, and Web of Science (2000-2024) identified original studies reporting L-R signaling in chordoma. Data on experimental models, signaling axes, functional assays, and clinical correlations were extracted using a predefined template. Evidence for each axis was graded as level A (causal/functional validation), level B (protein or spatial confirmation), or level C (inferred transcriptomic evidence). The review followed PRISMA-ScR and JBI scoping methodology.

resultsThirty studies met inclusion criteria. Ten recurrent signaling circuits were identified. Receptor tyrosine kinase pathways-EGF → EGFR and PDGF → PDGFR-were the most consistently validated, supported by multi-modal experimental evidence and limited clinical activity. IL-6 → IL-6R → STAT3 emerged as a stromal-immune-tumor axis with level A functional validation, linking CAF and macrophage activation to tumor invasion. TGF-β → TGFβR signaling and the newly defined ER-stress CAF-derived IER2 → GMFG → ITGB1 axis were supported by single-cell/spatial profiling with early functional evidence. PD-1/PD-L1 expression showed consistent prognostic correlations but lacked mechanistic validation.

conclusionThis review provides the first evidence-weighted map of intercellular signaling in chordoma. While RTK autocrine loops remain the most established, emerging cytokine- and CAF-mediated pathways highlight new biological mechanisms and potential therapeutic targets. Bridging single-cell discovery with functional validation and clinical translation will be essential to advance microenvironment-directed therapies in chordoma.

Indexed as

ChordomaSignal TransductionHumansLigandsStromal CellsTumor MicroenvironmentLigandsChordomaCytokine pathwayIntercellular signalingLigand–receptor interactionStromal crosstalkTumor microenvironment

Identifiers

PMID41965872
PMCPMC13195942

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Registered trials

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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.