Intraoperative glucocorticoids confound surgical biopsy transcriptomics

Abstract

Human tissue transcriptomic studies frequently rely on biopsies obtained during surgery under general anesthesia, yet the impact of perioperative medications on gene expression has not been systematically evaluated. Using paired liver biopsies from patients with obesity at risk for metabolic dysfunction-associated steatohepatitis (MASH), we compared RNA sequencing profiles from biopsies collected under local anesthesia months before surgery with matched intraoperative biopsies obtained under general anesthesia. Intraoperative samples exhibited striking transcriptional changes enriched for canonical glucocorticoid receptor target genes, implicating perioperative dexamethasone administration as the principal driver. In a matched cohort in which dexamethasone was administered immediately after biopsy collection, we directly demonstrate that dexamethasone profoundly alters hepatic gene expression during surgery. These findings were independently validated and shown to substantially distort associations between liver fibrosis stage and inflammatory gene expression, obscuring biologically relevant immune signatures. Similar glucocorticoid-responsive transcriptional changes were observed in adipose tissue, indicating a systemic effect. Our findings identify perioperative dexamethasone exposure as a previously unrecognized but readily modifiable confounder in human tissue transcriptomics. As biopsy-based bulk and single-cell transcriptomic studies continue to expand, careful documentation and consideration of perioperative medication exposure will be essential to improve the reproducibility, interpretability, and biological validity of human gene expression studies.

Concomitant Robotic Pericardial Window and Mediastinal Tumour Biopsy Under Intraoperative Ultrasound Guidance
Alfonso Fiorelli, Vincenzo Di Filippo, Antimo Leva +1
Interdisciplinary Cardiovascular and Thoracic Surgery12 Sep 2026Peer-reviewedCC BY-NC 4.0Full textCardiovascular medicinePMC
Functional and Structural Neuroanatomic Correlates of Intraoperative Anesthetic Dose-Adjusted EEG Alpha Power Among Older Surgical Patients
Tyler Reekes, Jeffrey N Browndyke, Melody Reese Smith +9
medRxiv21 Oct 2026PreprintAll rights reservedFull textSurgery & anaesthesiamedRxivPMC
Multimodality imaging for surgical decision-making in tricuspid regurgitation: from referral to intraoperative assessment.
Ahmed Ghazy, Till Humbert, Mohamad Albitar +6
European heart journal. Imaging methods and practice29 Sep 2026Peer-reviewedCC BY-NCFull textCardiovascular medicineEurope PMCPMC
Pulmonary epithelioid hemangioendothelioma with pleural dissemination: a case report of prolonged diagnostic delay and the role of surgical biopsy.
Rui Yan, Weiwei Feng, Lu Lu +2
BMC pulmonary medicine1 Jul 2026Peer-reviewedCC BY-NC-NDFull textOncologyEurope PMCDOAJ
Unilateral biportal endoscopic (UBE) posterior cervical foraminotomy utilizing intraoperative navigation: surgical technique.
Eli W Bunzel, Cyrus Emami, Alexander Kucherina +6
Journal of spine surgery (Hong Kong)22 Oct 2026Peer-reviewedCC BY-NC-NDFull textSurgery & anaesthesiaEurope PMC

Cite

BibTeX RIS

BibTeX

@misc{larsen2026intraoperative,
  title = {{Intraoperative glucocorticoids confound surgical biopsy transcriptomics}},
  author = {F. T. Larsen and C. W. Wernberg and J. Nambiar and S. Dutta and E. J. Nielsen and L. L. Groenkjaer and B. G. Jacobsen and S. Mandrup and A. Loft and S. F. Schmidt and M. E. M. Lauridsen and K. Ravnskjaer and L. Groentved},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.08.26362140},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.08.26362140v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Intraoperative glucocorticoids confound surgical biopsy transcriptomics
AU  - F. T. Larsen
AU  - C. W. Wernberg
AU  - J. Nambiar
AU  - S. Dutta
AU  - E. J. Nielsen
AU  - L. L. Groenkjaer
AU  - B. G. Jacobsen
AU  - S. Mandrup
AU  - A. Loft
AU  - S. F. Schmidt
AU  - M. E. M. Lauridsen
AU  - K. Ravnskjaer
AU  - L. Groentved
PY  - 2026
DA  - 2026/09/08
PB  - medRxiv
DO  - 10.64898/2026.09.08.26362140
UR  - https://www.medrxiv.org/content/10.64898/2026.09.08.26362140v1
AB  - Human tissue transcriptomic studies frequently rely on biopsies obtained during surgery under general anesthesia, yet the impact of perioperative medications on gene expression has not been systematically evaluated. Using paired liver biopsies from patients with obesity at risk for metabolic dysfunction-associated steatohepatitis (MASH), we compared RNA sequencing profiles from biopsies collected under local anesthesia months before surgery with matched intraoperative biopsies obtained under general anesthesia. Intraoperative samples exhibited striking transcriptional changes enriched for canonical glucocorticoid receptor target genes, implicating perioperative dexamethasone administration as the principal driver. In a matched cohort in which dexamethasone was administered immediately after biopsy collection, we directly demonstrate that dexamethasone profoundly alters hepatic gene expression during surgery. These findings were independently validated and shown to substantially distort associations between liver fibrosis stage and inflammatory gene expression, obscuring biologically relevant immune signatures. Similar glucocorticoid-responsive transcriptional changes were observed in adipose tissue, indicating a systemic effect. Our findings identify perioperative dexamethasone exposure as a previously unrecognized but readily modifiable confounder in human tissue transcriptomics. As biopsy-based bulk and single-cell transcriptomic studies continue to expand, careful documentation and consideration of perioperative medication exposure will be essential to improve the reproducibility, interpretability, and biological validity of human gene expression studies.
ER  -

Abstract

Related

Cite