Evidence map›Paper›PMID 41936612›Full record

ArticleScientific reports2026

IL-11-IL6ST-STAT3 signaling defines a convergent inflammatory axis in esophageal cancer subtypes.

Shayaq Ul Abeer Rasool, Arshad A Pandith, Farooq Ahmad Ganie, Qurat Ul Aein, Usma Manzoor, Dil Afroze, Aadil Manzoor Baba, Zubaida Rasool, Nazir Ahmad Dar, Showkeen Muzamil

Abstract read
In one paragraph

Article in Scientific reports, 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

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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

10 authors.

Shayaq Ul Abeer RasoolAdvanced Center for Human Genetics, Sher I Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Arshad A PandithAdvanced Center for Human Genetics, Sher I Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India. arshaajiz@gmail.com.
Farooq Ahmad GanieDepartment of Cardiovascular and Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Qurat Ul AeinAdvanced Center for Human Genetics, Sher I Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Usma ManzoorAdvanced Center for Human Genetics, Sher I Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Dil AfrozeAdvanced Center for Human Genetics, Sher I Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Aadil Manzoor BabaDepartment of Biochemistry, University of Kashmir, Srinagar, J&K, 190006, India.
Zubaida RasoolDepartment of Pathology, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, 190011, India.
Nazir Ahmad DarDepartment of Biochemistry, University of Kashmir, Srinagar, J&K, 190006, India.
Showkeen MuzamilDepartment of Biochemistry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Shuhama, J&K, India.

Funding

Indian Council of Medical Research 5/3/8/72/2020-ITR
6 · The paper itself

Abstract

Esophageal cancer (EC) is an aggressive malignancy characterized by poor survival outcomes and strong links to chronic inflammatory signaling. Interleukin-11 (IL-11) has emerged as a cytokine of interest in tumorigenesis and therapy resistance. This study investigated the expression, prognostic implications and functional relevance of IL-11 signaling in EC. IL-11 pathway components were analyzed in 50 surgically resected EC and adjacent normal tissues using RT-qPCR and immunohistochemistry (IHC). Histological subtype-stratified analyses were performed for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Functional assays in KYSE-410 cells evaluated the effect of IL-11 neutralization on viability, migration, and pathway activation. RNA-sequencing, reverse-phase protein array (RPPA), clinical, and survival data from the TCGA-ESCA cohort were analyzed to validate pathway activation and prognostic associations. Additionally, murine RNA-sequencing datasets following anti-IL-11 or anti-IL-11 receptor treatment were examined to assess downstream transcriptional effects. IL-11, COX-2, and STAT3 mRNA levels were significantly upregulated in tumors compared with matched normal epithelium (p < 0.05) accompanied by increased nuclear phosphorylation of STAT3 (Tyr705). TCGA analyses confirmed elevated expression of IL-11 pathway components in EC. Elevated IL11 expression showed a trend toward reduced overall survival and was significantly associated with poorer disease-free survival. While IL11, STAT3, and PTGS2 expression did not differ significantly between EAC and ESCC, receptor-level signaling components IL6ST (gp130) and JAK1 were significantly higher in EAC, with RPPA data demonstrating increased pSTAT3 (Tyr705) and e-cadherin levels in this subtype. Downstream transcriptional analyses revealed subtype-specific STAT3 programs, with proliferation and invasion genes enriched in ESCC and survival-associated mediators elevated in EAC. Neutralization of IL11 significantly reduced cell viability (IC50 = 1 µg/mL), impaired migration, and suppressed pSTAT3 activation. These findings identify the IL-11/IL6ST/JAK1/STAT3/COX-2 axis as a central inflammatory signaling pathway in esophageal cancer. Although ligand expression is comparable across subtypes, receptor-level signaling in EAC suggests pathway sensitization rather than ligand abundance as a key determinant of signaling intensity. Functional inhibition of IL-11 attenuates tumor-promoting phenotypes, supporting IL-11 signaling as a biologically relevant and potentially pan-histologic therapeutic target in esophageal cancer.

Indexed as

AdenocarcinomaCytokine Receptor gp130Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaInterleukin-11Signal TransductionSTAT3 Transcription FactorAgedAnimalsCell Line, TumorCell MovementCyclooxygenase 2FemaleGene Expression Regulation, NeoplasticHumansInflammationCyclooxygenase 2Cytokine Receptor gp130IL11 protein, humanIL6ST protein, humanInterleukin-11STAT3 protein, humanSTAT3 Transcription FactorCOX-2Cytokine signalingEsophageal cancerInflammationInterleukin-11STAT3Targeted therapy

Identifiers

PMID41936612
PMCPMC13212602

What Socratic holds

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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 Socratic graph.