SEPT9和PAI-1是肝细胞癌免疫微环境的免疫组化生物标志物。

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

作者信息

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

机构信息

Pathology and Laboratory Medicine, Albany Medical Center, 47 New Scotland Avenue, Albany, NY, Mail Code 8112208, USA.

Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Discov Oncol. 2025 Apr 7;16(1):483. doi: 10.1007/s12672-025-02252-5.

DOI:10.1007/s12672-025-02252-5

PMID:40192891

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11977054/

Abstract

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.

摘要

背景

Septin 9（SEPT9）与多种致癌蛋白相互作用，在包括肝细胞癌（HCC）在内的多种癌症中异常表达。纤溶酶原激活物抑制剂-1（PAI-1）通过调节肿瘤免疫微环境促进肿瘤形成和进展。CXCR2+免疫细胞在HCC的形成、进展和预后中起关键作用。SEPT9与PAI-1之间的关系及其对HCC免疫微环境的影响尚不清楚。

方法

通过免疫组织化学（IHC）评估76例HCC及背景良性肝脏组织中SEPT9和PAI-1的表达水平。检查它们的IHC结果与免疫细胞标志物（CXCR2、CD3、CD15、CD68和CD163）、临床参数和生存结果之间的关系。

结果

高级别HCC更频繁地表达SEPT9和PAI-1。SEPT9和PAI-1的表达相互关联。与PAI-1（-）的HCC相比，PAI-1（+）的HCC肿瘤内CXCR2、CD3、CD15、CD68和CD163的表达更高，而SEPT9的表达与肿瘤中更多的CXCR2+和CD15+细胞计数相关。SEPT9（+）的HCC患者总生存期较短，尽管SEPT9不是独立的预后因素。