Scholarlink

Background <p>Gastric adenocarcinoma (GAC) exhibits marked interpatient heterogeneity. Compact, biologically interpretable signatures linked to tumor–immune contexture may aid reproducible risk stratification and hypothesis generation for therapeutic responsiveness.</p> Methods <p>TCGA-GAC RNA-seq (<i>n</i> = 407; 375 tumors, 32 normals) was analyzed with limma to identify DEGs (<i>p</i> &lt; 1 × 10⁻³, |log₂FC|&gt;1). ImmPort overlap yielded immune DEGs, which were interaction-expanded via STRING to construct an immune-enriched candidate set for unsupervised co-expression analysis. WGCNA on expressed candidates identified co-expression modules; modules most associated with the tumor phenotype were prioritized for network centrality analysis, survival screening (maxstat), and multivariable Cox modeling to derive an immune-related gene prognostic index (IRGPI).</p> Results <p>XRCC2, NUSAP1, and ZWILCH were retained as independent prognostic factors and combined into IRGPI (0.526·XRCC2 + 0.581·NUSAP1 − 0.498·ZWILCH). IRGPI significantly stratified overall survival in TCGA with modest discrimination (time-dependent AUC ≈ 0.55) and showed reproducible stratification in GSE26942 (AUC ≈ 0.63). CIBERSORT-based deconvolution identified three TME clusters with distinct survival patterns. IRGPI groups differed in in silico–inferred immunotherapy-related features (TIDE-derived metrics and PD-L1/MDSC/T-cell dysfunction signatures) and in predicted cisplatin/gemcitabine sensitivity by pRRophetic.</p> Conclusions <p>This three-gene IRGPI provides a compact, biologically anchored risk stratification signal in GAC and is associated with computationally inferred immune contexture and therapy-related signatures. These associations are hypothesis-generating and require validation in treatment-annotated cohorts, particularly gastric cancer patients receiving immune checkpoint inhibitors; robustness to alternative gene-selection strategies should also be evaluated in future work.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Identification of a biologically coherent three gene immune signature predictive of immunotherapy benefit in gastric adenocarcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月14日

查看全文
  • Ruihua Fan,
  • Jiru Wang,
  • Lijuan Xu,
  • Yan Jin

摘要

Background

Gastric adenocarcinoma (GAC) exhibits marked interpatient heterogeneity. Compact, biologically interpretable signatures linked to tumor–immune contexture may aid reproducible risk stratification and hypothesis generation for therapeutic responsiveness.

Methods

TCGA-GAC RNA-seq (n = 407; 375 tumors, 32 normals) was analyzed with limma to identify DEGs (p < 1 × 10⁻³, |log₂FC|>1). ImmPort overlap yielded immune DEGs, which were interaction-expanded via STRING to construct an immune-enriched candidate set for unsupervised co-expression analysis. WGCNA on expressed candidates identified co-expression modules; modules most associated with the tumor phenotype were prioritized for network centrality analysis, survival screening (maxstat), and multivariable Cox modeling to derive an immune-related gene prognostic index (IRGPI).

Results

XRCC2, NUSAP1, and ZWILCH were retained as independent prognostic factors and combined into IRGPI (0.526·XRCC2 + 0.581·NUSAP1 − 0.498·ZWILCH). IRGPI significantly stratified overall survival in TCGA with modest discrimination (time-dependent AUC ≈ 0.55) and showed reproducible stratification in GSE26942 (AUC ≈ 0.63). CIBERSORT-based deconvolution identified three TME clusters with distinct survival patterns. IRGPI groups differed in in silico–inferred immunotherapy-related features (TIDE-derived metrics and PD-L1/MDSC/T-cell dysfunction signatures) and in predicted cisplatin/gemcitabine sensitivity by pRRophetic.

Conclusions

This three-gene IRGPI provides a compact, biologically anchored risk stratification signal in GAC and is associated with computationally inferred immune contexture and therapy-related signatures. These associations are hypothesis-generating and require validation in treatment-annotated cohorts, particularly gastric cancer patients receiving immune checkpoint inhibitors; robustness to alternative gene-selection strategies should also be evaluated in future work.