Polyribonucleotide phosphorylase is overexpressed in hepatocellular cancer, promoting epithelial phenotype maintenance and tumor progression

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-11-08 DOI:10.1016/j.prp.2024.155713

Francisco Revert-Ros , Ignacio Ventura , Jesús A. Prieto-Ruiz , Eduardo Giner-Moreno , Ángela Pérez-Cervera , Judith Pérez-Rojas , Fernando Revert , José Miguel Hernández-Andreu

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引用次数: 0

Abstract

Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health challenge, largely associated with cirrhosis caused by various factors. Prognosis is often guided by molecular and histological classifications. In this study, expression of Polyribonucleotide Phosphorylase (PNPT1) in HCC was investigated to better understand its role in tumor behavior and patient outcomes. The expression of the corresponding protein PNPase was assessed in HCC tissue samples using immunohistochemistry, while RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed via OncoDB. Additionally, PNPT1 silencing in HepG2 cells was followed by gene and protein expression analysis. The results revealed that PNPT1 is overexpressed in HCC tumors, particularly in those expressing E-cadherin. Notably, silencing PNPT1 in HepG2 cells triggered a shift towards a mesenchymal phenotype. In HCC tissues, PNPT1 expression was linked to markers of epithelial phenotype, oxidative stress, and poor prognosis, especially in non-viral HCC cases. These findings suggest that PNPase may play a crucial role in the progression of well-differentiated HCC tumors, serving as a poor prognostic biomarker.

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多核苷酸磷酸酶在肝细胞癌中过度表达，促进上皮表型的维持和肿瘤的进展。

肝癌，尤其是肝细胞癌（HCC），是全球健康面临的一大挑战，主要与各种因素导致的肝硬化有关。预后通常以分子和组织学分类为指导。本研究调查了多核苷酸磷酸酶（PNPT1）在 HCC 中的表达，以更好地了解其在肿瘤行为和患者预后中的作用。研究采用免疫组化方法评估了 HCC 组织样本中相应蛋白 PNPase 的表达，并通过 OncoDB 分析了癌症基因组图谱（TCGA）中的 RNA-seq 数据。此外，还通过基因和蛋白质表达分析对 HepG2 细胞中的 PNPT1 进行了沉默。结果显示，PNPT1 在 HCC 肿瘤中表达过高，尤其是在表达 E-cadherin 的肿瘤中。值得注意的是，在 HepG2 细胞中沉默 PNPT1 会引发向间充质表型的转变。在 HCC 组织中，PNPT1 的表达与上皮表型、氧化应激和预后不良的标志物有关，尤其是在非病毒性 HCC 病例中。这些研究结果表明，PNPase 在分化良好的 HCC 肿瘤的进展过程中可能起着关键作用，是预后不良的生物标志物。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.