TMEM59L: A Novel Biomarker for Colon Adenocarcinoma Diagnosis and Treatment

Filho, A. M. et al. The GLOBOCAN 2022 cancer estimates: data sources, methods, and a snapshot of the cancer burden worldwide. Int. J. Cancer.156 (7), 1336-1346 (2025). Araghi, M. et al. Colon and rectal cancer survival in seven high-income countries 2010–2014: variation by age and stage at diagnosis (the ICBP SURVMARK-2 project). Gut 70 (1), 114–126 (2021). Ravichandran, S. N. et al. An updated review on molecular biomarkers in diagnosis and therapy of colorectal cancer. Curr. Cancer Drug Targets. 24 (6), 595–611 (2024). Elson, G. C. A. et al. BSMAP, a novel protein expressed specifically in the brain whose gene is localized on chromosome 19p12. Biochem. Biophys. Res. Commun. 264 (1), 55–62 (1999). Zheng, Q. et al. The Neuron-Specific protein TMEM59L mediates oxidative Stress-Induced cell death. Mol. Neurobiol. 54 (6), 4189–4200 (2016). Aoki, M., Segawa, H., Naito, M. & Okamoto, H. Identification of possible downstream genes required for the extension of peripheral axons in primary sensory neurons. Biochem. Biophys. Res. Commun. 445 (2), 357–362 (2014). Yuan, X. et al. Genomic characteristics of adipose-derived stromal cells induced into neurons based on single-cell RNA sequencing. Heliyon. 10 (12), e33079 (2024). Mannherz, O., Mertens, D., Hahn, M. & Lichter, P. Functional screening for proapoptotic genes by reverse transfection cell array technology. Genomics 87 (5), 665–672 (2006). Gao, D. et al. Expression of TMEM59L associated with radiosensitive in glioblastoma. J. Radiat. Res. 64 (5), 833–841 (2023). Yang, H. et al. An analysis of the gene expression associated with lymph node metastasis in colorectal cancer. Int. J. Genomics. 2023, 1–16 (2023). Shi, C. et al. Prognostic value of TMEM59L and its genomic and immunological characteristics in cancer. Front. Immunol. 13,1054157 (2022). Sun, D. et al. TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res. 49 (D1), D1420–D30 (2021). Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15(2), R29 (2014). Walter, W., Sánchez-Cabo, F. & Ricote, M. GOplot: an R package for visually combining expression data with functional analysis. Bioinformatics 31 (17), 2912–2914 (2015). Wu, T. et al. ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innov. 2(3),100141 (2021). Yu, G., Wang, L-G., Yan, G-R. & He, Q-Y. DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics 31 (4), 608–609 (2015). Hänzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinform. 14(1), 7-7 (2013). Jing, Y. et al. Diagnostics and immunological function of CENPN in human tumors: from pan-cancer analysis to validation in breast cancer. Translational Cancer Res. 14 (2), 881–906 (2025). Wang, Y. et al. Identification of GGT5 as a novel prognostic biomarker for gastric cancer and its correlation with immune cell infiltration. Front. Genet. 13, 810292 (2022). Zhu, H. et al. TUBA1C is a prognostic marker in Low-grade glioma and correlates with immune cell infiltration in the tumor microenvironment. Front. Genet. 12, 759953 (2021). Jiang, P. et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat. Med. 24 (10), 1550–1558 (2018). Kanehisa, M. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28 (1), 27–30 (2000). Kanehisa, M. Toward Understanding the origin and evolution of cellular organisms. Protein Sci. 28 (11), 1947–1951 (2019). Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: biological systems database as a model of the real world. Nucleic Acids Res. 53 (D1), D672–D7 (2025). Li, B., Lin, R., Hua, Y., Ma, B. & Chen, Y. Single–cell RNA sequencing reveals TMEM71 as an Immunomodulatory biomarker predicting immune checkpoint Blockade response in breast cancer. Discover Oncol. 16(1),1256 (2025). Liu, Q. & Liao, L. Identification of macrophage-related molecular subgroups and risk signature in colorectal cancer based on a bioinformatics analysis. Autoimmunity. 57(1), 2321908 (2024). Lee, I-S. et al. A blood-based transcriptomic signature for noninvasive diagnosis of gastric cancer. Br. J. Cancer. 125 (6), 846–853 (2021). Adam-Artigues, A. et al. Circulating miR-30b-5p levels in plasma as a novel potential biomarker for early detection of breast cancer. ESMO Open. 6(1), 100039 (2021). Garrido-Cano, I. et al. Circulating miR-99a-5p expression in plasma: A potential biomarker for early diagnosis of breast cancer. Int. J. Mol. Sci. 21, 19 (2020). Huang, Q. et al. Plasma extracellular Vesicles-Derived miR-99a-5p: A potential biomarker to predict early head and neck squamous cell carcinoma. Pathol. Oncol. Res. 28, 1610699 (2022). Zhu, J. et al. Different MiRNA expression profiles between human breast cancer tumors and serum. Front. Genet. 5(5),149 (2014). Liu, T. et al. Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget 7 (51), 85551–85563 (2016). Zhao, K. et al. Exosome-Mediated transfer of circ_0000338 enhances 5-Fluorouracil resistance in colorectal cancer through regulating MicroRNA 217 (miR-217) and miR-485-3p. Mol. Cell. Biol. 41(5), e00517-20 (2023). Gibson, G. et al. Unraveling the regulatory mechanisms underlying Tissue-Dependent genetic variation of gene expression. PLoS Genet. 8(1), e1002431 (2012). Song, P. et al. Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J. Hematol. Oncol. 17(1), 46 (2024). Sheng, Y-N. et al. Zeaxanthin induces apoptosis via ROS-Regulated MAPK and AKT signaling pathway in human gastric cancer cells. OncoTargets Therapy. 13 10995–11006 (2020). Stefani, C. et al. Growth Factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: where are we now? Int. J. Mol. Sci. 22, 19 (2021). Bakrim, S. et al. Recent advances and molecular mechanisms of TGF-β signaling in colorectal cancer, with focus on bioactive compounds targeting. Biomed. Pharmacother. 177, 116886 (2024). Xu, H. & Song, Y. Analyzing the functional roles and immunological features of chemokines in COAD. Int. J. Mol. Sci. 25(10), 5410 (2024). Hu, J. et al. Dynamic network biomarker of Pre-Exhausted CD8 + T cells contributed to T cell exhaustion in colorectal cancer. Front. Immunol. 12, 691142 (2021). Jiang, W. et al. Exhausted CD8 + T cells in the tumor immune microenvironment: new pathways to therapy. Front. Immunol. 11, 6225099 (2021). Ferkel, S. A. M., Holman, E. A., Sojwal, R. S., Rubin, S. J. S. & Rogalla, S. Tumor-Infiltrating immune cells in colorectal cancer. Neoplasia 59, 1010911 (2025). Kvedaraite, E. & Ginhoux, F. Human dendritic cells in cancer. Sci. Immunol. 7(70), eabm9409 (2022). Wei, J. et al. Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma. Front. Immunol. 15, 1291938 (2024). Wu, T. & Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett. 387, 61–68 (2017). He, X. & Xu, C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 30 (8), 660–669 (2020). Zhang, Y. & Zhang, Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol. Immunol. 17 (8), 807–821 (2020). Jin, Q. et al. A disintegrin and metalloproteinase 8 induced epithelial-mesenchymal transition to promote the invasion of colon cancer cells via TGF‐β/Smad2/3 signalling pathway. J. Cell. Mol. Med. 24 (22), 13058–13069 (2020). Wang, B., Tan, Z. & Guan, F. Tumor-Derived exosomes mediate the instability of cadherins and promote tumor progression. Int. J. Mol. Sci. 20(15), 3652 (2019).