Frontiers in Medical Science Research, 2026, 8(2); doi: 10.25236/FMSR.2026.080205.
Yingxun Hua1, Jianxin Lyu2
1College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
2Key Laboratory of Laboratory Medicine, Ministry of Education, College of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme in collagen cross-linking, is overexpressed in various solid tumors and plays an important role in tumor invasion and metastasis. However, the potential prognostic significance of PLOD2 in glioma remains unclear. Here, we analyzed PLOD2 expression across multiple cancer types using the GEPIA2, TIMER2.0, and UALCAN databases, and confirmed that PLOD2 expression was significantly elevated in glioma tissues compared to corresponding normal tissues. Furthermore, high PLOD2 expression was associated with poor prognosis in glioma patients. Additionally, we utilized the Chinese Glioma Genome Atlas (CGGA) to investigate the association between PLOD2 and the clinicopathological and molecular characteristics of glioma patients. Our findings revealed that PLOD2 expression was positively correlated with tumor malignancy (e.g., higher WHO grade). Further analysis of the biological role of PLOD2 in glioma indicated its involvement in multiple biological processes implicated in glioma development, including immune responses, inflammatory responses, and the regulation of defense responses within the immune system. Immune infiltration analysis using the CIBERSORT database uncovered correlations between high PLOD2 expression and the infiltration of various immune cell types, as well as immune checkpoints, in glioma. In summary, this study reveals that PLOD2 is a key molecule in the malignant progression of glioma, serving not only as a potential diagnostic biomarker for GBM but also as a promising novel therapeutic target for improving glioma treatment.
PLOD2, Glioma, Immune, Prognosis
Yingxun Hua, Jianxin Lyu. Upregulation of PLOD2 as a Potential Biomarker Associated with Poor Prognosis and Immune Infiltration in Glioma. Frontiers in Medical Science Research (2026), Vol. 8, Issue 2: 35-43. https://doi.org/10.25236/FMSR.2026.080205.
[1] Jackson CM, Choi J, Lim M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat Immunol[J]. 2019,20(9):1100-1109.
[2] You H, Geng S, Li S, et al. Recent advances in biomimetic strategies for the immunotherapy of glioblastoma. Biomaterials[J]. 2024,311:122694.
[3] Chen R, Smith-Cohn M, Cohen AL, et al. Glioma Subclassifications and Their Clinical Significance. Neurotherapeutics[J]. 2017,14(2):284-297.
[4] Weller M, Wen PY, Chang SM, et al. Glioma. Nat Rev Dis Primers[J]. 2024,10(1):33.
[5] Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev[J]. 2014,23(10):1985-1996.
[6] Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A[J]. 2013,110(10):4009-4014.
[7] Osswald M, Jung E, Sahm F, et al. Brain tumour cells interconnect to a functional and resistant network. Nature[J]. 2015,528(7580):93-98.
[8] Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol[J]. 2021,23(8):1231-1251.
[9] Wells RG. The role of matrix stiffness in regulating cell behavior. Hepatology[J]. 2008,47(4):1394-1400.
[10] van der Slot AJ, Zuurmond AM, Bardoel AF, et al. Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis. J Biol Chem[J]. 2003,278(42):40967-40972.
[11] Sada M, Ohuchida K, Horioka K, et al. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility. Cancer Lett[J]. 2016,372(2):210-218.
[12] Du H, Pang M, Hou X, et al. PLOD2 in cancer research. Biomed Pharmacother[J]. 2017,90:670-676.
[13] Noda T, Yamamoto H, Takemasa I, et al. PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection. Liver Int[J]. 2012,32(1):110-118.
[14] Eisinger-Mathason TS, Zhang M, Qiu Q, et al. Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis. Cancer Discov[J]. 2013,3(10):1190-1205.
[15] Kurozumi A, Kato M, Goto Y, et al. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. Int J Oncol[J]. 2016, 48(5):1837-1846.
[16] Tomczak K, Czerwińska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Pozn)[J]. 2015,19(1a):A68-A77.
[17] Zhao Z, Zhang KN, Wang Q, et al. Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients. Genomics Proteomics Bioinformatics[J]. 2021,19(1):1-12.
[18] Carithers LJ, Moore HM. The Genotype-Tissue Expression (GTEx) Project. Biopreserv Biobank[J]. 2015,13(5):307-308.
[19] Tang Z, Kang B, Li C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res[J]. 2019,47(W1):W556-w560.
[20] Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia[J]. 2017,19(8):649-658.
[21] Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res[J]. 2020,48(W1):W509-w14.
[22] Thul PJ, Lindskog C. The human protein atlas: A spatial map of the human proteome. Protein Sci[J]. 2018,27(1):233-244.
[23] Chen B, Khodadoust MS, Liu CL, et al. Profiling Tumor Infiltrating Immune Cells with CIBERSORT. Methods Mol Biol[J]. 2018,1711:243-59.
[24] Murugan AK, Alzahrani AS. Isocitrate Dehydrogenase IDH1 and IDH2 Mutations in Human Cancer: Prognostic Implications for Gliomas. Br J Biomed Sci[J]. 2022,79:10208.
[25] Figarella-Branger D, Colin C, Mokhtari K, et al. Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: Lessons from the French POLA cohort. Neuro Oncol[J]. 2025,27(3):755-766.
[26] Fridman WH, Zitvogel L, Sautès-Fridman C, et al. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol[J]. 2017,14(12):717-734.
[27] Quail DF, Joyce JA. The Microenvironmental Landscape of Brain Tumors. Cancer Cell[J]. 2017,31(3):326-341.
[28] Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods[J]. 2015,12(5):453-457.
[29] Ostrom QT, Patil N, Cioffi G, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017. Neuro Oncol[J]. 2020,22(12 Suppl 2):iv1-iv96.
[30] Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol[J]. 2021,18(3):170-186.
[31] Juratli TA, Schackert G, Krex D. Current status of local therapy in malignant gliomas--a clinical review of three selected approaches. Pharmacol Ther[J]. 2013,139(3):341-358.
[32] Huang B, Zhang J, Zong W, et al. Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies. Front Immunol[J]. 2023,14:994698.