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Updated: Jan 7, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Identification and validation of tumor microenvironment-related therapeutic targets in gastric cancer using
Mohamed Kalith Oli M1, Jafar Ali Ibrahim Syed Masood2
1School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India.
Introduction:
With increased drug resistance and tumor heterogeneity accounting for limited therapeutic strategies, gastric cancer remains one of the major causes of cancer-related mortality around the globe. Targeting the components of the tumor microenvironment (TME) has become a promising therapeutic strategy due to their crucial roles in cancer cell proliferation, progression, and metastasis. One of the limitations of the previously identified therapeutic targets is their limited applicability to a broader patient population.
Methods:
This study aims to identify (TME)-related therapeutic targets using an integrated bioinformatics and molecular docking approach that involves a larger number of datasets to cover a broader cohort of gastric cancer patients. It analyzed multiple publicly available transcriptomic datasets using Robust Rank Aggregation (RRA) meta-analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to identify significant hub genes. Furthermore, protein-protein interaction (PPI) network analyses, conducted using multiple methods such as Cytohubba topology analysis and ClusterONE module analysis, refined the potential therapeutic candidates. Functional enrichment analyses were performed to identify vital genes involved in TME interactions and ECM remodeling.
Results:
The enriched genes were validated for their significant dysregulation in the Cancer Genome Atlas gastric adenocarcinoma dataset (TCGA-STAD) and three independent GEO datasets to ensure differential expression across distinct cohorts. Genes with consistent dysregulation were used in survival analyses across TCGA and two GEO datasets to prioritize hub genes with prognostic significance. Finally, a targeted literature survey ensured the exclusion of previously targeted genes, and molecular docking analyses conducted using phytocompounds identified potential therapeutic leads with strong affinities for the identified targets.
Discussion:
This integrated approach revealed notable, promising targets in the TME and natural compounds for developing potential personalized therapeutic strategies in gastric cancer.
Insights
This study identifies novel tumor microenvironment (TME) targets and natural compounds for gastric cancer therapy. The integrated bioinformatics approach aims to improve personalized treatment strategies for a wider patient population.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- Gastric cancer poses a significant global health challenge due to drug resistance and tumor heterogeneity.
- Targeting the tumor microenvironment (TME) offers a promising therapeutic avenue for cancer treatment.
- Existing TME targets have limited applicability across diverse patient groups.
Purpose of the Study:
- To identify novel TME-related therapeutic targets for gastric cancer using an integrated bioinformatics and molecular docking approach.
- To analyze a broad cohort of gastric cancer patients by incorporating multiple transcriptomic datasets.
- To discover potential phytocompound-based therapeutic leads for personalized gastric cancer treatment.
Main Methods:
- Utilized Robust Rank Aggregation (RRA) and Weighted Gene Co-expression Network Analysis (WGCNA) on public transcriptomic datasets.
- Performed protein-protein interaction (PPI) network analyses (Cytohubba, ClusterONE) to refine potential targets.
- Validated gene dysregulation in TCGA-STAD and GEO datasets, followed by survival analyses and molecular docking.
Main Results:
- Identified significant hub genes within the TME, with consistent dysregulation across multiple datasets.
- Prioritized prognostic hub genes through survival analyses, excluding previously targeted genes.
- Discovered phytocompounds with strong binding affinities to identified TME targets via molecular docking.
Conclusions:
- The integrated approach successfully identified promising TME targets and natural compounds for gastric cancer.
- This study lays the groundwork for developing personalized therapeutic strategies in gastric cancer.
- The findings offer potential new avenues for combating drug resistance and tumor heterogeneity in gastric cancer.
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