TPD52L2 在头颈部鳞状细胞癌中的过表达：预后意义及与免疫浸润的相关性。

Overexpression of TPD52L2 in HNSCC: prognostic significance and correlation with immune infiltrates.

机构信息

The Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.

The Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.

出版信息

BMC Oral Health. 2024 Oct 7;24(1):1191. doi: 10.1186/s12903-024-04977-1.

DOI:10.1186/s12903-024-04977-1

PMID:39375696

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11460091/

Abstract

BACKGROUND

Evidence has been presented that the tumor protein D52 (TPD52) family plays a critical role in tumor development and progression. As a member of the TPD52 family, the changes in TPD52L2 gene status are instrumental in kinds of cancer development. However, its effects on patient prognosis and immune infiltration in Head and Neck Squamous Carcinoma (HNSCC) are still poorly understood.

METHODS

The Tumor Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and c-BioPortal database was used to explore the expression pattern, prognostic value, and variation of gene status in HNSCC. The LinkedOmics database was used to obtain the co-expression genes of TPD52L2 and identify the diagnostic value of TPD52L2 in HNSCC. The correlations between TPD52L2 expression and six main types of immune cell infiltrations and immune signatures were explored using Tumor Immune Estimation Resource (TIMER). The correlation between TPD52L2 expression and immune checkpoint genes (ICGs) was analyzed by TCGA database. Immunohistochemistry (IHC) was performed to validate the expression of three ICGs (PDL1, PDL2, EGFR) and TPD52L2 using 5 paired HNSCC and normal head and neck tissues. Polymerase Chain Reaction (PCR) and Western Blot (WB) of HNSCC and normal head and neck cell lines were performed to verify the high level of TPD52L2 mRNA and protein expression. protein expression of TPD52L2 in pan-cancer was also validated using UALCAN.

RESULTS

TPD52L2 was overexpressed in tumor tissues, and it predicted worse survival status in HNSCC. ROC analysis suggested that TPD52L2 had a diagnostic value. Multivariate Cox analysis identified TPD52L2 as an independent negative prognostic marker of overall survival. Functional network analysis suggested that TPD52L2 was associated with immune-related signaling pathways, cell migration pathways, and cancer-related pathways. High expression of TPD52L2 was associated with a more mutant frequency of TP53. Notably, we found that the expression of TPD52L2 was closely negatively correlated with the infiltration levels of 15 types of immune cells and positively correlated with several immune markers. PCR, WB experiments, and UALCAN database verified the high level of TPD52L2 mRNA and protein expression.

CONCLUSION

TPD52L2 is upregulated in HNSCC, which is an independent factor for adverse prognosis prediction. It probably plays a role in the negative regulation of immune cell infiltration. TPD52L2 might be a promising prognostic biomarker and therapeutic target in HNSCC.

摘要

背景

有证据表明，肿瘤蛋白 D52（TPD52）家族在肿瘤的发生和发展中起着关键作用。作为 TPD52 家族的一员，TPD52L2 基因状态的变化对多种癌症的发展至关重要。然而，其对头颈部鳞状细胞癌（HNSCC）患者预后和免疫浸润的影响仍知之甚少。

方法

使用肿瘤基因组图谱（TCGA）、基因表达综合数据库（GEO）和 c-BioPortal 数据库来探讨 HNSCC 中 TPD52L2 基因状态的表达模式、预后价值和变化。使用 LinkedOmics 数据库获得 TPD52L2 的共表达基因，并确定 TPD52L2 在 HNSCC 中的诊断价值。使用肿瘤免疫估计资源（TIMER）探讨 TPD52L2 表达与六种主要类型免疫细胞浸润和免疫特征之间的相关性。通过 TCGA 数据库分析 TPD52L2 表达与免疫检查点基因（ICGs）的相关性。使用 5 对 HNSCC 和正常头颈部组织进行免疫组织化学（IHC）验证 TPD52L2 及三个 ICGs（PDL1、PDL2、EGFR）的表达。使用 HNSCC 和正常头颈部细胞系进行聚合酶链反应（PCR）和 Western Blot（WB）验证 TPD52L2 mRNA 和蛋白的高表达。使用 UALCAN 验证 TPD52L2 在泛癌中的表达。

结果

TPD52L2 在肿瘤组织中高表达，并且预测 HNSCC 患者的生存状态较差。ROC 分析表明 TPD52L2 具有诊断价值。多因素 Cox 分析确定 TPD52L2 是总生存的独立负预后标志物。功能网络分析表明，TPD52L2 与免疫相关信号通路、细胞迁移通路和癌症相关通路有关。TP53 的突变频率较高与 TPD52L2 的高表达相关。值得注意的是，我们发现 TPD52L2 的表达与 15 种免疫细胞浸润水平密切负相关，与几种免疫标志物呈正相关。PCR、WB 实验和 UALCAN 数据库验证了 TPD52L2 mRNA 和蛋白的高表达。