PPIH Expression Correlates with Tumor Aggressiveness and Immune Dysregulation in Hepatocellular Carcinoma

被引：0

作者：

Bei, Jiaxin ^{[1
,2
]}

Sun, Zihao ^{[1
,2
]}

Fu, Rongdang ^{[3
]}

Huang, Xinkun ^{[4
,5
]}

Huang, Jiabai ^{[4
,5
]}

Luo, Yongyou ^{[6
]}

Li, Yihu ^{[7
]}

Chen, Ye ^{[4
,5
]}

Wei, Zhisheng ^{[8
]}

机构：

[1] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Sch Clin Med 1, Dept Immunooncol, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Guangdong Prov Engn Res Ctr Esophageal Canc Precis, Guangzhou 510080, Guangdong, Peoples R China

[3] First Peoples Hosp Foshan, Dept Hepat Surg, Foshan 528000, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Affiliated Hosp 2, Dept Minimally Invas Intervent Radiol, Lab Intervent Radiol, Guangzhou 510260, Guangdong, Peoples R China

[5] Guangzhou Med Univ, Affiliated Hosp 2, Dept Radiol, Guangzhou 510260, Guangdong, Peoples R China

[6] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Sch Clin Med 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China

[7] Guangzhou Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Guangzhou 510260, Guangdong, Peoples R China

[8] Guangdong Pharmaceut Univ, Neurol Res Inst Integrated Tradit Chinese & Wester, Sch Clin Med 1, Dept Neurol,Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China

来源：

JOURNAL OF HEPATOCELLULAR CARCINOMA | 2024年 / 11卷

基金：

中国国家自然科学基金;

关键词：

hepatocellular carcinoma; PPIH; bioinformatics analysis; immune infiltration; Th17/Treg cell; CYCLOPHILIN-B; CANCER; CELL;

D O I：

10.2147/JHC.S492420

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Hepatocellular Carcinoma (HCC) features a complex pathophysiology and unpredictable immunosuppressive microenvironment, which limit the effectiveness of traditional therapies and lead to poor patient outcomes. Understanding the immune characteristics of HCC is essential for elucidating the immune microenvironment and developing more effective treatments. This study investigates the role of Peptidyl-prolyl isomerase H (PPIH) in HCC by analyzing its expression, prognosis, methylation levels, and relationship with immune cell infiltration. Methods: We utilized bulk sequencing and clinical data from UCSC Xena and the GTEx database for preprocessing and subsequent differential expression analysis of PPIH in tumor and adjacent normal tissues, evaluating prognostic parameters like overall survival and disease-free interval between low and high PPIH expression groups. Immune infiltration was analyzed via CIBERSORT and ssGSEA, while DNA methylation and somatic mutation analyses were performed using MExpress and "maftools", respectively, alongside in vitro and in vivo experiments to assess PPIH's functional roles. Results: Our findings indicated that PPIH is significantly upregulated in various cancer types, correlating with poor patient prognosis, increased somatic mutations, and altered gene methylation patterns. High PPIH levels were linked to enhanced T regulatory (Treg) cell infiltration and a decline in Th17 cell populations, impacting vital pathways related to DNA damage repair and tumor proliferation. Furthermore, PPIH knockdown in vitro led to reduced cell viability, proliferation, and invasion while promoting apoptosis. In vivo, PPIH knockdown repressed tumor growth and modified the immune microenvironment by attenuating Th17 cell infiltration and potentially increasing Treg cell accumulation. Conclusion: This study emphasizes PPIH's critical role in HCC progression by facilitating tumor growth and survival while modulating the immune landscape, thereby positioning PPIH as a potential therapeutic target for HCC management.

引用

页码：2453 / 2470

页数：18

共 51 条

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