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Background <p>Septin 9 (SEPT9) interacts with multiple oncogenic proteins and is expressed abnormally in several cancers, including hepatocellular carcinoma (HCC). Plasminogen activator inhibitor-1 (PAI-1) promotes tumor formation and progression by modulating the tumor immune microenvironment. CXCR2+ immune cells play a crucial role in HCC formation, progression, and prognosis. The&#xa0;relationship between SEPT9 and PAI-1, and their impact on the HCC immune microenvironment remains unclear.</p> Methods <p>Expression levels of SEPT9 and PAI-1 were evaluated by immunohistochemistry (IHC) in HCC and background benign liver (n = 76). Their IHC results were examined for relationships with immune cell markers (CXCR2, CD3, CD15, CD68, and CD163), clinical parameters, and survival outcomes.</p> Results <p>Higher grade HCC expressed SEPT9 and PAI-1 more frequently. SEPT9 and PAI-1 expression were associated with each other. PAI-1(+) HCCs had higher intratumoral CXCR2, CD3, CD15, CD68, and CD163 expression compared to PAI-1(−) HCCs, while SEPT9 expression correlated with greater CXCR2+ and CD15+ cell counts in tumor. SEPT9(+) HCC patients had shorter OS, although SEPT9 was not an independent prognostic factor.</p> Conclusion <p>SEPT9 is associated with PAI-1, a pro-tumorigenic protein. Both SEPT9 and PAI-1 are linked to advanced HCC grades. SEPT9 and PAI-1 positive HCCs have distinct CXCR2+ immune cell landscapes. Further investigation is needed to elucidate a possible SEPT9/PAI-1 interaction and the clinical utility of SEPT9 IHC in HCC.</p>

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SEPT9 and PAI-1 are immunohistochemical biomarkers of the hepatocellular carcinoma immune microenvironment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月7日

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  • Eundong Park,
  • Xin Wang,
  • Nusret Bekir Subasi,
  • Michel Kmeid,
  • Paul J. Higgins,
  • Anne Chen,
  • Hwajeong Lee

摘要

Background

Septin 9 (SEPT9) interacts with multiple oncogenic proteins and is expressed abnormally in several cancers, including hepatocellular carcinoma (HCC). Plasminogen activator inhibitor-1 (PAI-1) promotes tumor formation and progression by modulating the tumor immune microenvironment. CXCR2+ immune cells play a crucial role in HCC formation, progression, and prognosis. The relationship between SEPT9 and PAI-1, and their impact on the HCC immune microenvironment remains unclear.

Methods

Expression levels of SEPT9 and PAI-1 were evaluated by immunohistochemistry (IHC) in HCC and background benign liver (n = 76). Their IHC results were examined for relationships with immune cell markers (CXCR2, CD3, CD15, CD68, and CD163), clinical parameters, and survival outcomes.

Results

Higher grade HCC expressed SEPT9 and PAI-1 more frequently. SEPT9 and PAI-1 expression were associated with each other. PAI-1(+) HCCs had higher intratumoral CXCR2, CD3, CD15, CD68, and CD163 expression compared to PAI-1(−) HCCs, while SEPT9 expression correlated with greater CXCR2+ and CD15+ cell counts in tumor. SEPT9(+) HCC patients had shorter OS, although SEPT9 was not an independent prognostic factor.

Conclusion

SEPT9 is associated with PAI-1, a pro-tumorigenic protein. Both SEPT9 and PAI-1 are linked to advanced HCC grades. SEPT9 and PAI-1 positive HCCs have distinct CXCR2+ immune cell landscapes. Further investigation is needed to elucidate a possible SEPT9/PAI-1 interaction and the clinical utility of SEPT9 IHC in HCC.