Ubiquitous Aberration in Cholesterol Metabolism across Pancreatic Ductal Adenocarcinoma

Venugopal Gunda, Thiago C. Genaro-Mattos, Jyoti B. Kaushal, Ramakanth Chirravuri-Venkata, Gopalakrishnan Natarajan, Kavita Mallya, Paul M. Grandgenett, Karoly Mirnics, Surinder K. Batra, Zeljka Korade, Satyanarayana Rachagani

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens.

Original languageEnglish (US)
Article number47
JournalMetabolites
Volume12
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

Keywords

  • Dhcr24
  • Dhcr7
  • Free cholesterol
  • PDAC
  • Sterol analysis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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