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<p>As the core scaffold of the GAP Activity Toward Rags 2 complex (GATOR2) complex, <i>SEC13</i> regulates mTORC1 signaling and endoplasmic reticulum homeostasis to modulate cellular metabolism, exhibits elevated expression across various solid tumors driving malignant progression, yet its comprehensive molecular mechanisms and immunotherapeutic potential remain to be systematically elucidated. We conducted a comprehensive cancer analysis of <i>SEC13</i> using the TCGA and GEO databases to assess its expression, diagnostic importance, and prognostic relevance in different tumor types. We further investigated its genetic alterations, methylation modifications, and correlations with the immune microenvironment, and predicted potential molecular pathways through enrichment analysis. Specifically in breast cancer (BRCA), we validated <i>SEC13</i> protein expression levels in tumor tissues by Western blotting; comprehensively analyzed the effects of <i>SEC13</i> on BRCA cell proliferation, invasion, and migration capabilities using CCK-8, Transwell invasion, and cell scratch assays; and performed final validation at the protein level using tissue microarrays combined with immunohistochemistry. <i>SEC13</i> was significantly overexpressed across the majority of tumor types relative to matched normal tissues and exhibited stage-specific expression patterns. Furthermore, <i>SEC13</i> demonstrated substantial diagnostic potential in multiple malignancies; notably, its elevated expression served as an independent prognostic biomarker for breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and sarcoma (SARC). Bioinformatics analysis revealed that <i>SEC13</i> mutations were widely distributed across pan-cancer datasets and correlated with prognosis. Notably, <i>SEC13</i> expression positively correlated with m6A methylation while its promoter region showed hypomethylation. Furthermore, high <i>SEC13</i> expression was positively associated with immunogenomic markers but accompanied by a low immune infiltration phenotype. Functional experiments confirmed that <i>SEC13</i> enhances cell proliferation, invasion, and migration in BRCA. This study, through comprehensive bioinformatics integration and functional validation in BRCA, suggests that <i>SEC13</i> expression was correlated with tumor epigenetic modification-related processes (including m6A methylation and promoter DNA methylation) and immune microenvironment homeostasis in multiple malignancies, which provided correlative evidence for the potential involvement of <i>SEC13</i> in tumor epigenetic and immune regulation. Its expression profile may serve as a potential pan-cancer prognostic indicator for molecular stratification and prognostic evaluation, providing preliminary exploratory insights for subsequent research on <i>SEC13</i>-related tumor regulatory mechanisms. Notably, the current in vivo validation using NCG immunodeficient mice focuses on tumor cell-intrinsic malignant phenotypes, and direct verification of immune regulatory effects requires follow-up experiments in immunocompetent or humanized mouse models.</p>

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Integrated pan cancer analysis with breast cancer validation identifies SEC13 homolog as prognostic biomarker and immunotherapy target

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月13日

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  • Haojie Fu,
  • Jiawei Zhao,
  • Yiyang Wang,
  • Yongxiang Li,
  • Haocong Li,
  • Reyima Geni,
  • Boen Sun,
  • Chenming Guo

摘要

As the core scaffold of the GAP Activity Toward Rags 2 complex (GATOR2) complex, SEC13 regulates mTORC1 signaling and endoplasmic reticulum homeostasis to modulate cellular metabolism, exhibits elevated expression across various solid tumors driving malignant progression, yet its comprehensive molecular mechanisms and immunotherapeutic potential remain to be systematically elucidated. We conducted a comprehensive cancer analysis of SEC13 using the TCGA and GEO databases to assess its expression, diagnostic importance, and prognostic relevance in different tumor types. We further investigated its genetic alterations, methylation modifications, and correlations with the immune microenvironment, and predicted potential molecular pathways through enrichment analysis. Specifically in breast cancer (BRCA), we validated SEC13 protein expression levels in tumor tissues by Western blotting; comprehensively analyzed the effects of SEC13 on BRCA cell proliferation, invasion, and migration capabilities using CCK-8, Transwell invasion, and cell scratch assays; and performed final validation at the protein level using tissue microarrays combined with immunohistochemistry. SEC13 was significantly overexpressed across the majority of tumor types relative to matched normal tissues and exhibited stage-specific expression patterns. Furthermore, SEC13 demonstrated substantial diagnostic potential in multiple malignancies; notably, its elevated expression served as an independent prognostic biomarker for breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and sarcoma (SARC). Bioinformatics analysis revealed that SEC13 mutations were widely distributed across pan-cancer datasets and correlated with prognosis. Notably, SEC13 expression positively correlated with m6A methylation while its promoter region showed hypomethylation. Furthermore, high SEC13 expression was positively associated with immunogenomic markers but accompanied by a low immune infiltration phenotype. Functional experiments confirmed that SEC13 enhances cell proliferation, invasion, and migration in BRCA. This study, through comprehensive bioinformatics integration and functional validation in BRCA, suggests that SEC13 expression was correlated with tumor epigenetic modification-related processes (including m6A methylation and promoter DNA methylation) and immune microenvironment homeostasis in multiple malignancies, which provided correlative evidence for the potential involvement of SEC13 in tumor epigenetic and immune regulation. Its expression profile may serve as a potential pan-cancer prognostic indicator for molecular stratification and prognostic evaluation, providing preliminary exploratory insights for subsequent research on SEC13-related tumor regulatory mechanisms. Notably, the current in vivo validation using NCG immunodeficient mice focuses on tumor cell-intrinsic malignant phenotypes, and direct verification of immune regulatory effects requires follow-up experiments in immunocompetent or humanized mouse models.