PDCL3 是一种与肝癌免疫浸润相关的预后生物标志物。

PDCL3 is a prognostic biomarker associated with immune infiltration in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, Pudong Hospital Affiliated to Fudan University, 2800 Gongwei Road Pudong, Shanghai, 201399, People's Republic of China.

Department of Endocrinology, Pudong Hospital Affiliated to Fudan University, 2800 Gongwei Road Pudong, Shanghai, 201399, People's Republic of China.

出版信息

Eur J Med Res. 2024 Mar 17;29(1):177. doi: 10.1186/s40001-024-01787-7.

DOI:10.1186/s40001-024-01787-7

PMID:38494503

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10946092/

Abstract

BACKGROUND

Phosducin-like 3 (PDCL3) is a member of the photoreceptor family, characterized by a thioredoxin-like structural domain and evolutionary conservation. It plays roles in angiogenesis and apoptosis. Despite its significance, research on the biological role of PDCL3 in liver hepatocellular carcinoma (LIHC) remains limited. This study aims to explore the prognostic value and potential mechanisms of PDCL3 in cancer, particularly in LIHC, through bioinformatics analysis.

METHODS

RNA-seq data and corresponding clinical information for pan-cancer and LIHC were extracted from the TCGA database to analyze PDCL3 expression and survival prognosis. Differential expression of PDCL3 was analyzed using the HPA database. GO and KEGG enrichment analysis were performed for PDCL3-associated genes. The relationship between PDCL3 expression and various immune cell types was examined using the TIMER website. Clinical samples were collected, and immunohistochemistry and immunofluorescence experiments were conducted to validate the differential expression of PDCL3 in LIHC and normal tissues. In vitro assays, including CCK-8, wound healing, Transwell, and colony formation experiments, were employed to determine the biological functions of PDCL3 in LIHC cells.

RESULTS

Analysis from TIMER, GEPIA, UALCAN, and HPA databases revealed differential expression of PDCL3 in various tumors. Prognostic analysis from GEPIA and TCGA databases indicated that high PDCL3 expression was associated with poorer clinical staging and prognosis in LIHC. Enrichment analysis of PDCL3-associated genes revealed its involvement in various immune responses. TCGA and TIMER databases showed that high PDCL3 expression in LIHC decreased tumor immune activity by reducing macrophage infiltration. PDCL3 exhibited positive correlations with multiple immune checkpoint genes. Immunohistochemistry (IHC) and immunofluorescence (IF) experiments confirmed elevated PDCL3 expression in LIHC tissues compared to adjacent normal tissues. In vitro experiments demonstrated that PDCL3 promoted LIHC cell proliferation, migration, invasion, and colony-forming ability.

CONCLUSION

PDCL3 is highly expressed in various cancer types. Our study suggests that elevated PDCL3 expression in hepatocellular carcinoma is associated with poorer prognosis and may serve as a potential diagnostic biomarker for LIHC. PDCL3 may regulate the biological functions of LIHC by modulating immune infiltration. However, the precise regulatory mechanisms of PDCL3 in cancer warrant further investigation.

摘要

背景

Phosducin-like 3（PDCL3）是感光细胞家族的成员，其特征是具有硫氧还蛋白样结构域和进化保守性。它在血管生成和细胞凋亡中发挥作用。尽管 PDCL3 具有重要意义，但关于其在肝癌（LIHC）中的生物学作用的研究仍然有限。本研究通过生物信息学分析旨在探讨 PDCL3 在癌症中的预后价值和潜在机制，特别是在 LIHC 中。

方法

从 TCGA 数据库中提取泛癌和 LIHC 的 RNA-seq 数据和相应的临床信息，以分析 PDCL3 表达和生存预后。使用 HPA 数据库分析 PDCL3 的差异表达。对 PDCL3 相关基因进行 GO 和 KEGG 富集分析。使用 TIMER 网站检查 PDCL3 表达与各种免疫细胞类型的关系。收集临床样本，进行免疫组织化学和免疫荧光实验，验证 LIHC 和正常组织中 PDCL3 的差异表达。体外实验包括 CCK-8、划痕愈合、Transwell 和集落形成实验，用于确定 PDCL3 在 LIHC 细胞中的生物学功能。

结果

从 TIMER、GEPIA、UALCAN 和 HPA 数据库的分析表明，PDCL3 在各种肿瘤中的表达存在差异。从 GEPIA 和 TCGA 数据库的预后分析表明，LIHC 中高 PDCL3 表达与较差的临床分期和预后相关。PDCL3 相关基因的富集分析表明，它参与了各种免疫反应。TCGA 和 TIMER 数据库显示，LIHC 中 PDCL3 的高表达通过减少巨噬细胞浸润降低了肿瘤免疫活性。PDCL3 与多种免疫检查点基因呈正相关。免疫组织化学（IHC）和免疫荧光（IF）实验证实，与相邻正常组织相比，LIHC 组织中 PDCL3 的表达升高。体外实验表明，PDCL3 促进了 LIHC 细胞的增殖、迁移、侵袭和集落形成能力。