Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of PLOD2

Abstract

Some previous studies have shown that PLOD2 has some value in tumorigenesis. However, the broad significance of PLOD2 has not been discussed in depth. This study was aimed at elaborated and summarized the value of PLOD2 in various tumors. First, we integrated GTEx, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases to analyze the expression of PLOD2, and found that it was expressed differently in normal tissues and significantly highly expressed in most tumors compared with normal tissues. Second, our analysis revealed that PLOD2 expression was negatively correlated with the prognosis of several tumors. For gastric cancer, the median overall survival time was significantly higher in the PLOD2 low expression group [HR 0.616 (95%CI 0.442–0.858), p = 0.004]. Third, for tumor immunity, PLOD2 was significantly associated with tumor infiltration, including immune infiltrating cells; immune checkpoint expression; immune microenvironment scores (immune score, stromal score and estimate scores); immunotherapy-related scores (tumor mutational burden, microsatellite instability, tumor neoantigen burden); expression of DNA repair genes Mismatch Repairs and methyltransferase; and enrichment analyses identified PLOD2-associated terms and pathways. Lastly, twenty pairs of gastric cancer and adjacent immunohistochemistry showed that PLOD2 was significantly overexpressed in gastric cancer (p < 0.001). Collectively, PLOD2 played a significant role in tumorigenesis and maybe serve as a potential biomarker for diagnosis and prognosis in cancers.

PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma

“…PLOD2 was later found to be involved in immune infiltration in different cancer cell types(F. 11 ; Q. 12 ; B. 10 ).…”

METTL3 facilitates renal cell carcinoma progression by PLOD2 m6A-methylation under prolonged hypoxia

“…M 6 A modifications on PLOD2 mRNA can be subsequently recognized by YTHDF1, an m 6 A reader, enhancing the translation of PLOD2 protein [ 16 ]. Enhanced PLOD2 expression activates key molecules in signalling pathways related to migration and invasion, thus promoting RCC development [ 11 ].…”

“…Hypoxic condition can stimulate various pathways in cancer cells, leading to dysregulation of genes and facilitating the progression of RCC. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a member of PLOD family (PLOD1, PLOD2, and PLOD3), mediates the formation of stabilized collagen cross-links [ 11 ]. PLOD2 has oncogenic roles and acts as a prognostic biomarker in several types of cancers [ 12 , 13 ].…”

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

“…In the same view, Xu et al. showed that PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2), a member of PLOD family which mediates the formation of stabilized collagen cross-links generating a stiffer ECM, is overexpressed in a variety of tumors including gastric, bladder, lung, breast, and head and neck squamous cell cancer ( 52 ). Notably, in GC, PLOD2 expression was negatively correlated with the presence of memory B cells, activated NK cells, plasma cells, CD8 + T cells, follicular helper T cells and Tregs; on the other hand, it was positively correlated with macrophages, activated mast cells, resting NK cells, CD4 memory activated T cells and CD4 memory resting T cells.…”