Gastric Cancer with Ovarian Metastasis Exhibits Distinct Transcriptomic and Pharmacogenomic Signatures Revealing Immune Metabolic Vulnerabilities

Ovarian metastasis from gastric cancer (GOM) represents a rare but clinically significant condition that poses major diagnostic and therapeutic challenges. Often misclassified as primary ovarian cancer (OC) due to morphological and anatomical similarities, GOM may be subjected to inappropriate treatment regimens that do not reflect its true biological characteristics. To address this gap, we conducted a comprehensive transcriptomic analysis using RNA-seq data from publicly available datasets, including GOM, primary gastric cancer (GC), OC, and normal ovarian tissues. Unsupervised clustering and principal component analysis revealed that GOM constitutes a transcriptionally distinct subtype, clearly separable from both GC and OC. Differential expression and enrichment analyses showed that GOM exhibits widespread immune suppression, including downregulation of MHC class II-mediated antigen presentation and T cell activation, as well as upregulation of metabolic and non-coding RNA pathways. Cross-comparison identified 54 consistently dysregulated genes, among which five hub genes (NR1H4, RHBG, ENPP6, ADAMTS9-AS1, and TCERG1L) were tightly linked to metabolic rewiring and immune evasion. In silico drug sensitivity prediction based on ssGSEA scores indicated that GOM is more responsive to agents such as Dinaciclib (CDK inhibitor), Romidepsin (HDAC inhibitor), SN-38 (Topoisomerase I inhibitor), and Sepantronium bromide (survivin inhibitor), compared to OC. These findings highlight the transcriptional autonomy and distinct pharmacologic vulnerabilities of GOM and provide a rationale for reclassifying it as a metastasis-adapted entity with specific therapeutic needs. Our results support the development of molecular diagnostics and tailored therapies targeting GOM’s unique immune-metabolic axis.