Endocrine oncology

Plasma proteomic profiling identifies apolipoprotein A4 as a downregulated biomarker of adrenocortical carcinoma: a multi-platform discovery and validation study

Eur J EndocrinolPublished Biomarker discovery and validation study

Authors' conclusion

Across discovery, targeted, and orthogonal platforms, APOA4 consistently exhibited lower circulating levels in ACC, supporting its potential as a serum biomarker for the preoperative differentiation of ACC from ACA. External, multiethnic validation and clinically deployable assays, alone or within multimarker panels, are warranted.

Study context

Population
Patients with adrenocortical carcinoma (ACC) or adrenocortical adenoma (ACA) from a tertiary center; targeted validation in an expanded two-center cohort including Asan Medical Center
Comparison
ACC vs ACA
Outcome
Circulating protein biomarkers distinguishing ACC from ACA
Methodological detailsmulti-platform proteomics, stepwise discovery, verification, targeted and orthogonal validation, two-center targeted validation, Fasting plasma profiled by LC-MS/MS with data-independent acquisition; Differentially expressed proteins (DEPs) defined by t-tests with P < .05 and |fold-change| >1.2, Targeted validation by parallel reaction monitoring (PRM); orthogonal validation with Olink Explore 384 Inflammation II panel in an independent set
  • Multi-platform proteomics
  • Stepwise discovery, verification, targeted and orthogonal validation
  • Two-center targeted validation
  • Fasting plasma profiled by LC-MS/MS with data-independent acquisition; DEPs defined by t-tests with P < .05 and |fold-change| >1.2
  • Targeted validation by parallel reaction monitoring (PRM); orthogonal validation with Olink Explore 384 Inflammation II panel in an independent set

Performance

As reported in the abstract

Differentially expressed plasma proteins, ACC vs ACA

DEPs in discovery cohort (ACC = 10, ACA = 67)

67

22 upregulated and 45 downregulated in ACC

DEPs in verification cohort (ACC = 7, ACA = 11)

17

Olink (ACC = 15; ACA = 24): proteins differing between ACC and ACA after false discovery rate correction

40

Original publication

Plasma proteomic profiling identifies apolipoprotein A4 as a downregulated biomarker of adrenocortical carcinoma: a multi-platform discovery and validation study. Eur J Endocrinol. Published 7 May 2026. doi:10.1093/ejendo/lvag079

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