Comprehensive assessment of cleavage and polyadenylation specificity factors in hepatocellular carcinoma: Expression, prognostic significance and immune infiltration analysis

Lu,Yuxiang; Wang,Ting; Yan,Xiuli; Zhang,Hui

doi:10.3892/mco.2025.2855

Comprehensive assessment of cleavage and polyadenylation specificity factors in hepatocellular carcinoma: Expression, prognostic significance and immune infiltration analysis

Authors:
- Yuxiang Lu
- Ting Wang
- Xiuli Yan
- Hui Zhang
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Affiliations: Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: April 28, 2025 https://doi.org/10.3892/mco.2025.2855
Article Number: 60
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC), a prevalent and highly malignant form of liver cancer, poses significant global health challenges. Previous studies have suggested that alterations in cleavage and polyadenylation specificity factors (CPSFs) play a role in the development and prognosis of HCC. Despite these insights, a thorough evaluation of CPSFs' expression levels, prognostic value and association with immune infiltration in HCC is lacking. To address this gap, the present study conducted a systematic analysis leveraging multiple bioinformatics databases to elucidate the functions of CPSFs in HCC. To comprehensively investigate the role of CPSFs in HCC, a diverse array of bioinformatics tools and publicly accessible datasets were utilized. The present study investigated the gene expression patterns, clinicopathological correlations, and diagnostic and prognostic capabilities of CPSFs. Furthermore, genetic variations, co‑expression networks and the role of CPSFs in immune cell infiltration and tumor‑related pathways were examined. To elucidate the biological functions of CPSF‑associated genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were integrated. For experimental validation, reverse transcription‑quantitative polymerase chain reaction was used to assess gene expression and the Cell Counting Kit‑8 assay was utilized to evaluate the effects of CPSFs on HCC cell proliferation. Our analysis offers valuable insights into the molecular mechanisms through which CPSFs contribute to HCC progression. The current findings suggest that CPSFs, particularly CPSF1, CPSF3, CPSF4 and CPSF6, exhibit significant transcriptional upregulation in HCC, with their overexpression closely tied to advanced tumor progression. These CPSFs showed diagnostic and prognostic significance in HCC. Additionally, CPSF expression was associated with immune cell infiltration and activation status. Functional enrichment analysis indicated that CPSF1, CPSF3, CPSF4, CPSF6 and CPSF7 are involved in cancer‑related signaling pathways, highlighting their role in tumor immune modulation. Experimental validation demonstrated that the expression of CPSF3 and CPSF7 was notably greater in the HCC cell lines than in the normal liver cells. Knockdown of CPSF3 and CPSF7 inhibited HCC cell proliferation, suggesting their potential oncogenic roles. This research offers an in‑depth evaluation of the expression patterns, prognostic relevance and immune modulation‑related functions of CPSFs in HCC. The observed upregulation of CPSFs in HCC, coupled with their association with poor clinical outcomes and immune system activation, highlights their potential as prognostic indicators. Nonetheless, additional experimental studies are needed to fully elucidate the molecular mechanisms and clinical significance of CPSFs in HCC.

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