Evidence map›Paper›PMID 42787726›Full record

ArticleIranian journal of basic medical sciences2026

Identification of key genes and pathways involved in trastuzumab resistance in HER2-positive gastric cancer through integrative bioinformatics analysis.

Feng Wang, Negar Mottaghi-Dastjerdi, Fatma Altameemi, Behzad Shahbazi, Nahid Ahmadi, Hamed Montazeri, Mohammad Soltany-Rezaee-Rad, Mohammad-Javad Niazi, Fateme Yazdani, Hamed Morad and 1 more

Abstract read
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Article in Iranian journal of basic medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Feng WangHenan Key Laboratory of Medical Tissue Regeneration, Henan Medical University, Xinxiang, Henan 453003, China.
Negar Mottaghi-DastjerdiDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Fatma AltameemiDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Behzad ShahbaziSchool of Pharmacy, Semnan University of Medical Sciences, Semnan, Iran.
Nahid AhmadiSchool of Pharmacy, Semnan University of Medical Sciences, Semnan, Iran.
Hamed MontazeriDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Mohammad Soltany-Rezaee-RadBehestan Innovation Factory, Behestan Darou, Tehran, Iran.
Mohammad-Javad NiaziPharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Fateme YazdaniDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Hamed MoradDepartment of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Nana LiHenan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Henan Medical University, Xinxiang, Henan 453003, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Trastuzumab resistance limits therapeutic efficacy in HER2-positive gastric cancer, and its systems-level regulatory architecture remains poorly characterized. This study aimed to identify key regulatory modules, biomarkers, and candidate therapeutic targets associated with trastuzumab resistance. Materials and Methods: Gene expression profiles from trastuzumab-sensitive and -resistant gastric cancer cell lines (GSE77346) were analyzed to identify differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were constructed, and hub genes were identified using topology-based methods and clustering. Functional enrichment analysis was performed using Gene Ontology and KEGG pathways. Prognostic relevance was evaluated using TCGA-STAD data via UALCAN. Drug-gene interactions were explored using DrugBank and PHAROS, followed by structural modeling and molecular docking. Results: Trastuzumab resistance was linked to transcription factor-driven reprogramming, cytoskeletal and adhesion remodeling, and receptor tyrosine kinase (RTK) bypass signaling. Eleven hub genes were identified across four functional modules potentially associated with FGFR signaling, epithelial-mesenchymal transition (EMT), and lineage plasticity. Elevated PXDN and CDH2 expression was significantly associated with poor overall survival in TCGA-STAD. Molecular docking provided preliminary in silico evidence for potential interactions between selected compounds, including ADH-1, AGX51, artenimol, and phenethyl isothiocyanate, and candidate targets, including N-cadherin/CDH2, ID3, and vimentin. Conclusion: Trastuzumab resistance may involve networks related to transcriptional plasticity, adhesion dynamics, and RTK redundancy. This study provides a hypothesis-generating framework for future biomarker-guided combination strategies, which requires validation in HER2-positive cohorts and experimental models.

Indexed as

BioinformaticsBiomarkersDrug resistanceGastric cancerGene expression profilingHER2Protein interaction mapsTrastuzumab

Identifiers

PMID42787726
PMCPMC13602869

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.