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.
Highlights
The PLOD3 gene is critical for collagen synthesis, mutations are related with disorders of the connective tissue and the development of several tumor entities [1,2,5]
In most of the analyzed cancers, PLOD3 gene expression was significantly higher in tissues of cancer compared to its expression in healthy tissues (Figure 3)
The overexpression of the PLOD3 gene was further linked to poor clinical prognoses (e.g., adrenocortical carcinoma (ACC), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), Figure 5)
Summary
The expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) is essential for the biosynthesis of collagen and gene mutations thereof, and are related to disorders of the connective tissue [1,2,3]. Clinical related mutations with reduced expressions of the PLOD family are associated with the Ehlers-Danlos and Bruck syndromes [4,5,6]. PLOD3 alterations during tissue repair might, lead to epithelial–mesenchymal transition (EMT). This process describes the transformation of stable epithelial cells undertaking phenotypic transformation. EMT is a key process in wound healing, tissue repair and, in the development of a variety of cancers [7,8,9]
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