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SRSF7 is a promising prognostic biomarker in hepatocellular carcinoma and is associated with immune infiltration

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Abstract

Background

Previous studies indicate that the splicing process, regulated by the cellular machinery of tumors (spliceosome), undergoes alterations, leading to oncogenic splicing events associated with the progression of tumors towards aggressiveness. However, the role of serine/arginine-rich splicing factor 7 (SRSF7) in hepatocellular carcinoma (HCC) and the tumor microenvironment (TME) remains unclear.

Methods

This study was aimed to explore the role and clinical significance of SRSF7 in HCC. By conducting functional analysis and gene set enrichment analysis, it was discovered that SRSF7 contributes to multiple pathways associated with immune response and tumor advancement. Further experiments verified that silencing of SRSF7 obviously inhibits progression of HCC.

Results

Aberrant expression of SRSF7, which were referred as an independent prognostic risk factor, effectively predicts the prognosis of patients with HCC. Functional and gene enrichment analyses revealed that SRSF7 is linked with multiple immune and tumor progression-related pathways, including the B cell receptor signaling pathway, positive regulation of leukocyte and immunoglobulin receptor binding cell activation, nuclear division, membrane invagination, cell cycle, as well as mTOR signaling pathway. Furthermore, increased SRSF7 expression was associated with tumor-infiltrating inflammatory cells (CD4+, monocytes/macrophages, CD8 + and endothelial). Additionally, multiple immune checkpoint genes were markedly positively related to SRSF7. The efficiency of SRSF7 in predicting immunomodulator and chemokine responses were also assessed in microenvironment. Moreover, in vitro analyses demonstrated that knockdown of SRSF7 suppressed the malignant evolution of HCC possibly by deactivating the PI3K/AKT/mTOR signaling.

Conclusion

The role of SRSF7 in the tumor microenvironment has been successfully assessed. It may be a valid bio-index for predicting the HCC prognosis, thereby guiding individualized immunotherapy for cancer.

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Data availability

The authors certify that all the original data in this research could be obtained from a public database. All data generated or analyzed during this study are included in this article.

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Author notes

  1. Lebin Yuan and Fei Cheng authors are contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Wei Shen, Lebin Yuan, Fei Cheng, Zhao Wu & Xiaodong Li

Authors
  1. Wei Shen
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  2. Lebin Yuan
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  3. Fei Cheng
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  4. Zhao Wu
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  5. Xiaodong Li
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Contributions

LY and FC conducted the formal analysis and wrote the original draft; WS performed the project administration; LY, FC conducted the experiments. ZW and XL participated in software analysis; LY, FC, ZW, and XL conducted data curation; LY and FC contributed to writing, reviewing, and editing the article; All authors read and approved the final submitted manuscript.

Corresponding author

Correspondence to Wei Shen.

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Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

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Shen, W., Yuan, L., Cheng, F. et al. SRSF7 is a promising prognostic biomarker in hepatocellular carcinoma and is associated with immune infiltration. Genes Genom 46, 49–64 (2024). https://doi.org/10.1007/s13258-023-01463-w

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