Calcium sensing receptor expression is downregulated in gastroenteropancreatic neuroendocrine tumours via epigenetic mechanisms
2025

Calcium Sensing Receptor in Gastroenteropancreatic Neuroendocrine Tumors

Sample size: 64 publication 10 minutes Evidence: moderate

Author Information

Author(s): Katherine A. English, Michelle Goldsworthy, Brittannie Willis, Kreepa G. Kooblall, Shweta Birla, Andreas Selberherr, Mark Stevenson, Omair A. Shariq, Ann L. Oberg, Tony Wang, James Carmichael, Konstantinos Mavrommatis, Laure Escoubet, Rajesh V. Thakker, Sarah A. Howles, Kate E. Lines

Primary Institution: University of Oxford

Hypothesis

CaSR expression may be altered in GEP‐NETs as a result of epigenetic changes.

Conclusion

The study reveals that CaSR expression is decreased in GEP‐NETs due to DNA methylation and chromatin changes, indicating its role as a tumor suppressor.

Supporting Evidence

  • CASR mRNA expression was significantly higher in normal islets compared to gastrinomas, insulinomas, and NF-PNETs.
  • Immunohistochemical analysis confirmed a significant reduction in CaSR protein expression in all GEP-NET subtypes.
  • Transfection of wild type CaSR into QGP-1 cells decreased cell viability.

Takeaway

This study found that a protein called CaSR is not working well in certain tumors, which might help those tumors grow faster.

Methodology

The study used RNA-Scope, quantitative PCR, immunohistochemistry, and methylation analysis on tumor samples from two cohorts.

Limitations

The study only examined the epigenetic landscape of one cell line and did not include in vivo work.

Participant Demographics

Mean patient age was 71 years, with 67% female in the first cohort and 50% female in the second cohort.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1002/ijc.35264

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