Abstract
Transmembrane protein 59-like (TMEM59L) has been implicated in malignant tumors; however, its role in colon adenocarcinoma (COAD) remains poorly understood. This study aimed to investigate the diagnostic and prognostic potential of TMEM59L in COAD, explore its association with the tumor microenvironment (TME) and potential implications for immunotherapy response. TMEM59L expression was analyzed in COAD tissue and serum samples using data from TCGA and GEO. Validation was conducted through immunohistochemistry (tissue) and ELISA (serum). Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis; prognostic relevance was evaluated with Kaplan–Meier survival analysis, Cox regression, and nomograms. Functional enrichment analyses were performed to identify associated pathways. Immune cell infiltration was estimated using ssGSEA and single-cell data from TISCH. Immunotherapy response was predicted based on TIDE scores. In vitro, TMEM59L-overexpressing HCT116 cells were used to assess proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) using colony formation, Transwell, qPCR, and western blot assays. TMEM59L expression was significantly downregulated in COAD tissues but elevated in serum samples. High tissue expression was associated with advanced tumor stage and poorer overall survival. Genes co-expressed with TMEM59L were enriched in cancer-related and immune-regulatory pathways. Although TMEM59L expression correlated with increased immune infiltration and immune checkpoint gene expression, high levels predicted poorer response to immunotherapy. Cellular experiments demonstrated that TMEM59L overexpression enhanced proliferation, migration, invasion, and induced EMT (decreased E-cadherin; increased N-cadherin, VE-cadherin, and MMP14) in HCT116 cells. TMEM59L shows promise as a diagnostic and prognostic biomarker in COAD, with potential roles in modulating the TME, EMT, and immunotherapy response.
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The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Liaoning Provincial Scientific and Technological Plan Project(2023010789-JH3/108).
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JW: Writing–original draft, Conceptualization, Data curation, Methodology, Project administration, Software, Validation, Visualization, Writing–review & editing. YD: Writing–original draft, Data curation, Software, Visualization; WJ: Writing–review & editing, Conceptualization, Data curation, Validation; DZ: Writing–original draft, Conceptualization, Data curation, Methodology, Project administration, Software, Validation, Visualization, Writing–review & editing. CS: Writing–original draft, Conceptualization, Data curation, Fuding acquisition, Methodology, Project administration, Software, Supervision, Validation, Writing–review & editing.
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This study was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (Approval No: PJ-KS-KY-2024-100). All human tissue samples and associated clinicopathological data were collected retrospectively after obtaining informed consent from participants or their family members. All procedures conformed to the ethical standards of the institutional review board and the 1964 Helsinki Declaration and its later amendments. All personal identifiers were removed to ensure privacy and confidentiality.
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Wang, W., Jia, W., Du, Y. et al. Identification of TMEM59L as a potential diagnosis, prognosis and immunotherapy biomarker for colon adenocarcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36478-2
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DOI: https://doi.org/10.1038/s41598-026-36478-2
