Nault JC, Campani C, Hirsch TZ, Neumann E, Arif W, Imbeaud S, Baretti M, Ziol M, Sidali S, Roger P, Allaire M, Bouattour M, Marra F, Fresneau B, Llarch N, Peron JM, Gerolami R, Khac EN, Nahon P, Ganne-Carrié N, Caldéraro J, Beaufrère A, Paradis V, Guettier C; CAPRIH FFCD cohort; Sutton A, Yarchoan M, Zucman-Rossi J.
J Hepatol. 2026 Feb 5:S0168-8278(26)00055-3.
ntroduction: Fibrolamellar carcinoma (FLC) is a rare primary liver cancer that predominantly affects young patients with normal known serum tumor biomarkers. An observation of an elevated procalcitonin (PCT) in one patient prompted us to investigate PCT as a biomarker in a larger cohort of FLC.
Methods: We measured serum PCT levels in 34 samples from 18 patients with FLC and in 64 patients with hepatocellular carcinoma (HCC), 24 with cholangiocarcinoma (CCA), and 20 with cirrhosis. Using RNA sequencing, we analyzed CALCA expression, encoding PCT, in 27 FLC tumors, 331 HCC tumors, 39 CCA tumors, 71 hepatoblastomas, 34 hepatocellular adenomas, and 55 non-tumor livers. Spatial transcriptomics was performed on three FLC and PCT immunohistochemistry on 13 FLC and 34 other primary or secondary liver cancers.
Results: In 8 FLC from the European cohort, median serum PCT was significantly elevated (55.2 μg/l) compared to patients with HCC (0.14 μg/l), CCA (0.16 μg/l), and cirrhosis (0.11 μg/l; P=0.0005). It was validated in a U.S. cohort of 10 FLC patients compared to HCC and CCA (P=0.0002). Across these cohorts, elevated serum PCT was observed in 83% of FLC cases versus 3% of HCC and CCA (P<0.0001). In four patients, changes in serum PCT levels correlated with radiologic response according to RECIST 1.1. RNA sequencing demonstrated significant overexpression of CALCA in FLC compared to other primary liver tumors (P<0.0001), and spatial transcriptomics localized CALCA expression specifically to tumor cells. Immunohistochemistry confirmed PCT overexpression in 77% of FLC but not in other liver cancers.
Conclusion: Procalcitonin is a sensitive and specific serum biomarker for FLC among primary liver cancers, with potential utility in diagnosis and monitoring of treatment response.
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