Given the highly aggressive clinical features and the poor response to systematic therapy for fumarate hydratase deficient-renal cell carcinoma (FHDRCC), early determination of the fumarate hydratase (FH) status in renal tumors offers a great opportunity for radical surgical intervention in the initial stages of tumor development. Recently, a novel plasma marker, succinyl-adenosine (Suc-Ado), has been recognized for their ability to indicate FH-mutated status and reflect tumor burden in FHDRCC. This study aims to confirm the diagnostic values of this circulating biomarker.

We analyzed plasma samples from 9 patients with FHDRCC, diagnosed through surgical pathology and immunohistochemistry. Additionally, 20 plasma samples from patients with clear cell renal cell carcinoma (ccRCC) and 20 plasma samples from healthy donors were included as comparison groups. The plasma samples collected prior to nephrectomy were analyzed for Suc-Ado levels using triple-quadrupole liquid chromatography–mass spectrometry (LC–MS). We assessed the distribution of Suc-Ado levels across groups, using the Mann-Whitney U test for comparisons. Furthermore, we evaluated the effectiveness of Suc-Ado as a biomarker for FHDRCC by using the Receiver Operating Characteristic Area Under the Curve (ROCAUC).

We found significantly elevated levels of Suc-Ado in the plasma of patients with FHDRCC (mean=96.61 ng/mL; standard deviation (SD)=165.59 ng/mL) compared to the ccRCC group (mean=20.18 ng/mL; SD=6.32 ng/mL) (P value< 0.001) and the normal group (mean=13.1 ng/mL; SD=1.75 ng/mL) (P value= 0.008). In distinguishing FHDRCC from normal samples, Suc-Ado demonstrated a ROCAUC of 0.9944 (sensitivity=100%, specificity=95%, cutoff=15.85 ng/mL). When differentiating FHDRCC from ccRCC samples, Suc-Ado revealed a ROCAUC of 0.8028 (sensitivity= 88.89%, specificity=65%, cutoff=20.3 ng/mL). Moreover, we also found a correlation between the Suc-Ado levels and the size of the primary tumor (Spearman’s rho= 0.881, P value=0.004) in the 9 patients diagnosed with FHDRCC.

Our results concurred the potential of Suc-Ado as a powerful biomarker for FHDRCC not only from normal samples but also from other types of renal cell carcinoma. In addition, Suc-Ado could potentially serve as an indicator of tumor burden in FHDRCC.