ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunology and Therapeutic Innovations in Hepatocellular Carcinoma: Exploring Immune Evasion and BeyondView all 20 articles
A novel prognostic model for Hedgehog signaling pathway-related genes 1 predicts the prognosis of hepatocellular carcinoma 2
Provisionally accepted
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Background The Hedgehog signaling pathway is involved in the 11 carcinogenesis and development of liver cancer in hepatocellular 12 carcinoma(HCC); however, few studies on the prognostic model of the 13 Hedgehog signaling pathway have been found. 14 Methods 15 First, we selected 56 Hedgehog signaling pathway-related genes from the 16 UALCAN database and used the DESeq2method to screen out differentially 17 expressed genes in HCC and normal liver samples. Validation was 18 performed using quantitative real-time PCR (qRT-PCR) of HCC and normal 19 tissues. Second, the differentially expressed genes were analyzed using Cox 20 and Lasso regression, and a five-gene prognostic risk model was established. 21 Risk scores were divided into high-risk and low-risk groups, and their 22 correlation with clinical indicators and immunity was analyzed. Univariate 23 and multivariate regression analyses were performed for risk scores. Finally, 24 a comparative functional enrichment analysis was conducted to delineate the 25 biological pathway disparities between the high-and low-risk groups. The 26 effectiveness of the model was validated using the ICGC database. 27 Results The prognostic risk model of five genes(BMP2,CSNK1D,CSNK1E, 28 ZIC2, and PRKACB) was obtained after screening 56 Hedgehog signaling 29 pathway-related genes. Risk scores emerged as robust independent 30 predictors of overall survival through univariate and multivariate analyses, 31 independent of other clinicopathological parameters, in TCGA and ICGC 32 cohorts. A significant correlation was observed between risk scores and 33 immune microenvironment characteristics, including immune cell infiltration 34 and immune checkpoint expression levels. qRT-PCR analysis confirmed that 35 the expression of the five genes in the prognostic model was higher in HCC 36 tissues than in normal tissues. Moreover, some functional pathways were 37 identified in the high-risk group. 38 Conclusions We developed a novel five-gene prognostic model centered on 39 Hedgehog signaling pathway-related genes, which holds potential as a 40 valuable prognostic tool for HCC and may provide guidance for 41 immunotherapy selection.
Keywords: COX, Cox regression, HCC, Hedgehog signaling pathway-related genes, prognosis
Received: 28 Jul 2025; Accepted: 16 Dec 2025.
Copyright: © 2025 Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Wang
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