TY - JOUR
T1 - SEPT9 and PAI-1 are immunohistochemical biomarkers of the hepatocellular carcinoma immune microenvironment
AU - Park, Eundong
AU - Wang, Xin
AU - Subasi, Nusret Bekir
AU - Kmeid, Michel
AU - Higgins, Paul J.
AU - Chen, Anne
AU - Lee, Hwajeong
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
KW - CXCR2
KW - HCC
KW - PAI-1
KW - SEPT9
KW - Tumor microenvironment
UR - https://www.scopus.com/pages/publications/105003092631
U2 - 10.1007/s12672-025-02252-5
DO - 10.1007/s12672-025-02252-5
M3 - Article
C2 - 40192891
AN - SCOPUS:105003092631
SN - 2730-6011
VL - 16
JO - Discover Oncology
JF - Discover Oncology
IS - 1
M1 - 483
ER -