Sonic hedgehog expression in steatohepatitic hepatocellular carcinoma and its clinicopathological significance

Hedgehog (Hh) signaling pathway dysregulation is involved in the pathogenesis of metabolic dysfunction-associated steatohepatitis, and the sonic Hh (SHh) protein, a pivotal molecule in the Hh pathway, is expressed in ballooned hepatocytes. The present study aimed to investigate the clinicopathological significance of SHh expression in steatohepatitic hepatocellular carcinoma (SH‑HCC). Reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry were performed to examine SHh gene and SHh protein expression in SH‑HCC. Additionally, patients with conventional HCC (C‑HCC) were included in the control group. Comparisons of patient and tumor characteristics were also performed. The prevalence of SH‑HCC was 3% in the whole cohort, and it was significantly associated with a high prevalence of diabetes mellitus. SHh mRNA was detected in all patients with SH‑HCC, but not in 23% of patients with C‑HCC. Notably, SHh mRNA expression was not significantly different between patients with SH‑HCC and those with C‑HCC; however, high SHh protein expression was significantly more frequent in SH‑HCC patients than in those with C‑HCC. Although the prognosis was not significantly different between the SH‑HCC and C‑HCC groups, high SHh protein expression was an independent poor prognostic factor for HCC. In conclusion, SHh could potentially serve as a therapeutic target for patients with HCC.