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June 20, 2026Annals of Surgery

High NTSR1 expression linked to worse colorectal cancer survival by driving an immune-cold tumor microenvironment.

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Why the study?

Does high NTSR1 expression correlate with poor prognosis and immune exclusion in colorectal cancer?

Population

Colorectal cancer patients from The Cancer Genome Atlas and an independent surgical validation cohort from…

Comparison

NTSR1 antagonist SR48692 / High NTSR1 expression vs Low NTSR1 expression / Vehicle (in vitro)

Design

Cohort

Key result

High NTSR1 expression is an independent risk factor for progression-free interval and overall survival in colorectal cancer, driving an immune-cold, suppressive tumor microenvironment.

Authors

HWHaoming WuYWYang WangJSJun Song

Discussion

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Member takes

Overview

NTSR1 testing should not yet guide CRC care; leaves open targeted inhibition in immune-cold tumors.

Key Points

  • This research aims to elucidate the role of neurotensin receptor 1 in immune exclusion and tumor progression in colorectal cancer.
  • Integrated transcriptomic and clinical data from The Cancer Genome Atlas and an independent cohort.
  • Utilized Random Forest machine learning to identify features related to NTS/NTSR1 signaling.
  • Employed a 3D tumor spheroid co-culture model to assess T-cell distribution in relation to NTS/NTSR1 signaling.
  • High NTSR1 expression linked to increased risk of progression-free interval and overall survival in respective cohorts.
  • NTS/NTSR1 signaling alters a mechano-structural network, impacting tumor microenvironment composition.
  • 3D modeling showed that NTS/NTSR1 signaling limits T-cell infiltration, mitigated by the antagonist SR48692.

Study Design

Type

Cohort

Multicenter

Yes

Structured PICO

Does high NTSR1 expression correlate with poor prognosis and immune exclusion in colorectal cancer?

P
Population
Colorectal cancer patients from The Cancer Genome Atlas (discovery cohort) and an independent surgical validation cohort from the University of Kentucky, plus 3D tumor spheroid co-culture models.
E
Exposure
NTSR1 antagonist SR48692 (in vitro) / High NTSR1 expression (observational)
C
Comparator
Low NTSR1 expression / Vehicle (in vitro)
O
Outcome
Progression-free interval (discovery cohort) and overall survival (validation cohort); spatial T-cell distribution (in vitro)hard clinical

High NTSR1 expression defines an immune-cold, poor-prognosis colorectal cancer subtype, suggesting NTSR1 antagonism as a potential strategy to overcome immune exclusion.

Cite This Study

Wu et al. (2026) conducted a cohort in Colorectal cancer. High NTSR1 expression was evaluated on Progression-free interval and overall survival. High NTSR1 expression is an independent risk factor for progression-free interval and overall survival in colorectal cancer, driving an immune-cold, suppressive tumor microenvironment.

synapsesocial.com/papers/6a3721e201fe431c2518893fhttps://doi.org/10.1097/sla.0000000000007131
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