A Human Pan-Cancer System Analysis of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 (PLOD3)

Abstract

The overexpression of the enzymes involved in the degradation of procollagen lysine is correlated with various tumor entities. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) expression was found to be correlated to the progression and migration of cancer cells in gastric, lung and prostate cancer. Here, we analyzed the gene expression, protein expression, and the clinical parameters of survival across 33 cancers based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC), function annotation of the mammalian genome 5 (FANTOM5), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases. Genetic alteration, immune infiltration and relevant cellular pathways were analyzed in detail. PLOD3 expression negatively correlated with survival periods and the infiltration level of CD8+ T cells, but positively correlated to the infiltration of cancer associated fibroblasts in diverse cancers. Immunohistochemistry in colon carcinomas, glioblastomas, and soft tissue sarcomas further confirm PLOD 3 expression in human cancer tissue. Moreover, amplification and mutation accounted for the largest proportion in esophageal adenocarcinoma and uterine corpus endometrial carcinoma, respectively; the copy number alteration of PLOD3 appeared in all cancers from TCGA; and molecular mechanisms further proved the effect of PLOD3 on tumorigenesis. In particular, PLOD3 expression appears to have a tumor immunological effect, and is related to multiple immune cells. Furthermore, it is also associated with tumor mutation burden and microsatellite instability in various tumors. PLOD3 acts as an inducer of various cancers, and it could be a potential biomarker for prognosis and targeted treatment.

Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status

“…Results showed overexpression of two genes coding for lysyl hydroxylases, procollagen-lysine, and 2-oxoglutarate 5-dioxygenase (PLOD) [ 66 ], PLOD1 , and PLOD2 , involved in collagen biosynthesis and crosslinking [ 66 , 67 ] in LGG-IDH1 wt and GBM. Similar results were recently reported by other authors [ 68 , 69 ] and in other cancer types with aggressive phenotype [ 70 ]. We also found upregulation of another gene related to collagen biosynthesis, the serpin family H member 1 ( SERPINH1 ), which was significantly correlated with LOXL1 in LGG-IDH wt and GBM, and with LOX in GBM.…”

Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase Family: Novel Prognostic Biomarkers and Tumor Microenvironment Regulators for Lower-Grade Glioma

“…Our previous work indicated that PLOD3 overexpression is linked to poor prognosis in LGG and is associated with immune cell infiltration of the TME (Gong et al, 2021). In this study, a comprehensive analysis of the correlation between specific PLOD family members (e.g., PLOD1, PLOD2, and PLOD3) and LGG has been performed using the CGGA and TCGA datasets.…”

“…It has recently been recognized that PLOD1 is overexpressed in glioma (Tian et al, 2021). Our previous work demonstrated that PLOD3 is also highly expressed in LGG with a poor prognosis (Gong et al, 2021). Here, we focused on the regulation of the TME and prognostic functions of the PLOD family in LGG.…”

PLODs: Novel prognostic biomarkers and potential immunotherapy targets for head and neck squamous cell carcinoma

“…The PLOD family includes PLOD1, PLOD2, and PLOD3, all of which may be linked to various cancers, including gastric cancer, sarcoma, and liver cancer [ [18] , [19] , [20] ]. Our previous work reported that PLOD3 likely acts as an oncogene, and overexpression of this protein may lead to various tumors [ 21 ]. In addition, changes in the expression of the PLOD family have been linked to lower grade glioma (LGG) and soft tissue sarcoma and could be a regulator of the TME [ 22 , 23 ].…”