Open Access

ARTICLE

Development and Assessment of a Novel Palmitoylation-Related lncRNA Signature for Prognosis and Immune Landscape in Hepatocellular Carcinoma

Zhilong He^1,#, Jing Qin^1,#, Sixuan Wu^2,#, Xian Liang¹, Yu Liu¹, Jinfeng Qiu¹, Zhimin Li^2,*, Kai Hu^1,*

1 Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
2 Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China

* Corresponding Authors: Zhimin Li. Email: ; Kai Hu. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Long noncoding RNAs as Tumorigenic Drivers and Therapeutic Targets)

Oncology Research 2026, 34(2), 18 https://doi.org/10.32604/or.2025.070567

Received 18 July 2025; Accepted 26 September 2025; Issue published 19 January 2026

Abstract

Objective: The contribution of long non-coding RNAs (lncRNAs) associated with protein palmitoylation to the progression of hepatocellular carcinoma (HCC) remains largely unclear. This study sought to establish a prognostic signature based on palmitoylation-related lncRNAs and explore their functional implications in HCC. Methods: RNA sequencing and clinical data for HCC and normal tissues were sourced from the Cancer Genome Atlas (TCGA). Pearson correlation analysis was used to identify lncRNAs that were co-expressed with palmitoylation-related genes. Univariate Cox regression was applied to select lncRNAs with prognostic value, followed by the construction of a predictive model using the least absolute shrinkage and selection operator (LASSO) regression. A focused analysis was performed on one key lncRNA, AC009403.1. Expression levels of the final nine lncRNAs included in the model were further validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: A prognostic model for HCC was developed using nine palmitoylation-associated lncRNAs: AC009403.1, AC010789.1, AC026402.2, AC107021.2, AC135050.6, AL353572.4, MKLN1-AS, PRRT3-AS1, and ZNF582-AS1. This model effectively stratified patients into high- and low-risk groups exhibiting significantly different overall survival (OS) and progression-free survival (PFS), with the low-risk group showing more favorable outcomes. The high-risk group was associated with an immunosuppressive microenvironment, higher tumor mutation burden (TMB), and increased sensitivity to certain chemotherapeutic drugs (e.g., Sorafenib). Finally, RT-qPCR validation revealed that all nine lncRNAs were significantly upregulated in HCC tissues. Conclusion: The nine-lncRNA signature exhibits robust predictive power for HCC prognosis and provides novel insights into the mechanisms of lncRNA-regulated palmitoylation in HCC development.

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Supplementary Material

Supplementary Material File

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