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Pan-Cancer Analysis Identifies SEC11A as an Immunological and Prognostic Biomarker

Qingqing Wu, Chengdong Liu, Guangzhao Huang, Xinyan Lu, Xiaozhi Lv, Tingru Shao

Objective: Limited evidence suggests a vital role for SEC11A in carcinogenesis. Our study conducted an integrated analysis on the molecular features and clinical relevance of SEC11A across pan-cancer based on multi-omics data.

Materials and methods: SEC11A expression was analyzed in 33 types of tumor and normal specimens utilizing transcriptome profiles from The Cancer Genome Atlas-Genotype-Tissue Expression (TCGA-GTEx) project and protromic data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) project. Copy number alterations and methylation of SEC11A were investigated across pan-cancer with cBioPortal. Clinical relevance and prognostic implications of SEC11A were evaluated in The Cancer Genome Atlas (TCGA) cohorts. Gene Set Enrichment Analysis (GSEA) of SEC11A was conducted in Head and Neck Squamous Cell Carcinoma (HNSCC) with cluster profiler package. Correlation of SEC11A with immune cell infiltrations was estimated with Estimating the Proportions of Immune and Cancer cells (EPIC), Tumor Immune Estimation Resource (TIMER), xCELL, Microenvironment Cell Populations-counter (MCP-counter), quanTIseq, Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Immune Cell Abundance Identifier (ImmuCellAI) algorithms. Inhibitory Concentration (IC₅₀) values of anti-cancer agents were curated from Genomics of Drug Sensitivity in Cancer (GDSC) project and their correlations to SEC11A were calculated.

Results: We found the expression of SEC11A was upregulated in most of cancer types (24/33), while was downregulated in 3 types of cancers. Genetic amplification in SEC11A was widespread across pan-cancer. There were negative correlations of SEC11A Ribonucleic Acid (RNA) expression with methylation level. The upregulation of SEC11A indicated unfavorable prognosis in adrenocortical carcinoma and HNSCC. Moreover, SEC11A was closely involved in cell cycle, TP53 regulation and antigen processing. SEC11A was positively associated with tumor-associated macrophage and fibroblast but negatively associated with CD8⁺ T cell. The expression of SEC11A was positively correlated to drug resistance to anticancer drugs.

Conclusion: These findings suggested that SEC11A could act as a prognostic biomarker across pan-cancer. Upregulation of SEC11A was in relation to tumor immunosuppressive status. Collectively, our results offered a valuable resource that might guide mechanistic and therapeutic analysis of SEC11A across cancers.