Interplay between the cellular stress pathway, stemness markers, and Helicobacter pylori infection in gastric cancer

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-05-19 DOI:10.1016/j.genrep.2025.102263

Mehran Gholamin , Atena Mansouri , Mohammad Reza Abbaszadegan , Mohammad Ali Karimi , Hossein Barzegar , Fatemeh Fardi Golyan , Hanie Mahaki , Hamid Tanzadehpanah , Reihaneh Alsadat Mahmoudian

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引用次数: 0

Abstract

Background

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, particularly in regions with a high prevalence of Helicobacter pylori (H. pylori). Chronic H. pylori infection triggers persistent inflammation and cellular stress, both of which play critical roles in the malignant transformation of gastric epithelial cells. This study aimed to investigate the correlation between H. pylori infection, activation of cellular stress pathways, and the expression of stemness markers in GC.

Methods

The study analyzed GC tissues and matched adjacent normal tissues from 86 patients who underwent gastrectomy. Total RNA was extracted from these samples and subjected to quantitative real-time PCR to evaluate the mRNA expression profiling of stemness markers (CD44 and SALL4) and stress response proteins (DDIT3 or CHOP and GRP94 or HSP90B1). The presence of H. pylori was confirmed by PCR amplification of specific bacterial genes.

Results

The study revealed significant overexpression of CD44 (43/86) and SALL4 (49/86) in tumor tissues compared to adjacent normal tissues, with expression levels correlating with advanced disease stages (P < 0.05). Elevated expression of DDIT3 (32/86) and GRP94 (39/86) was also observed, highlighting their roles in apoptosis resistance and increased tumor aggressiveness (P < 0.05). Notably, a significant correlation was found between the co-expression of DDIT3, GRP94 (HSP90B1), CD44, and SALL4 with each other in relation to certain clinicopathological features in GC specimens (P < 0.05). Furthermore, H. pylori infection was detected in 55.8 % of samples, suggesting a strong association between chronic inflammation and GC progression.

Conclusion

These findings highlight the critical role of H. pylori-induced cellular stress in promoting stemness properties within GC cells. The upregulation of stemness markers presents promising potential as prognostic indicators and therapeutic targets. Understanding of these molecular mechanisms could facilitate the development of innovative diagnostic tools and targeted treatments for GC.

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胃癌细胞应激途径、茎干标记物与幽门螺杆菌感染的相互作用

背景胃癌（GC）仍然是世界范围内癌症相关死亡的主要原因之一，特别是在幽门螺杆菌（h.p ylori）高发地区。慢性幽门螺杆菌感染引发持续性炎症和细胞应激，这两者在胃上皮细胞的恶性转化中起关键作用。本研究旨在探讨幽门螺杆菌感染、细胞应激通路激活与胃癌干性标志物表达的相关性。方法对86例胃切除术患者的胃癌组织及相匹配的邻近正常组织进行分析。从这些样本中提取总RNA，并进行实时荧光定量PCR，评估干性标记（CD44和SALL4）和应激反应蛋白（DDIT3或CHOP、GRP94或HSP90B1）的mRNA表达谱。通过特异性细菌基因的PCR扩增证实了幽门螺杆菌的存在。结果研究发现，肿瘤组织中CD44（43/86）和SALL4（49/86）的过表达与邻近正常组织相比显著升高，且表达水平与疾病晚期相关(P <；0.05)。DDIT3（32/86）和GRP94（39/86）的表达也有所升高，这表明它们在细胞凋亡抵抗和肿瘤侵袭性增强中发挥了重要作用(P <；0.05)。值得注意的是，在GC标本中，DDIT3、GRP94 （HSP90B1）、CD44和SALL4的共表达与某些临床病理特征之间存在显著相关性(P <；0.05)。此外，55.8%的样本中检测到幽门螺杆菌感染，表明慢性炎症与GC进展之间存在很强的关联。结论幽门螺杆菌诱导的细胞应激在促进胃癌细胞的干性方面具有重要作用。干性标志物的上调作为预后指标和治疗靶点具有很大的潜力。了解这些分子机制有助于开发新的GC诊断工具和靶向治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.