Overexpressing PLOD Family Genes Predict Poor Prognosis in Pancreatic Cancer

Abstract

Background: Pancreatic cancer is a common malignant tumor. Multiple studies have shown that procollagen lysyl-hydroxylase (PLOD) family genes were closely related to tumor progression and metastasis in a variety of human cancers. This study aimed to explore the prognosis and biological role of PLOD family genes in pancreatic adenocarcinoma (PAAD). Methods: GEPIA, GEO, HPA, CCLE, Kaplan–Meier plotter, cBioPortal, LinkedOmics, DAVID6.8, STRING, and TIMER were employed to determine the prognostic values and biological function of PLOD family members in PAAD. Results: The mRNA and protein expression patterns of PLOD family members were noticeably up-regulated in PAAD compared with normal tissues. PLOD family gene expression was also up-regulated in pancreatic cancer cell lines. PLOD1 was correlated with histological and pathological grades of pancreatic cancer. PLOD2 was related to histological grade. The high expression of PLOD1-2 was correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. Additionally, PLODs showed high sensitivity and specificity in distinguishing pancreatic cancer from normal tissues. Through the functional enrichment analysis of PLOD-related genes in PAAD, we found that PLODs were enriched in collagen fiber tissue structure, lysine degradation, and collagen biosynthesis. Pathway analysis confirmed that PLODs regulated the proliferation, migration, and metastasis of pancreatic cancer through the RalGEF-Ral signaling pathway. Furthermore, the level of expression of PLOD1-2 was positively correlated with the activity of tumor-infiltrating immune cells, including CD8+T cells, neutrophils, macrophages, and dendritic cells. The level of expression of PLOD3 was inversely correlated with the level of infiltration of CD8+T cells. PLOD1 and PLOD2 were highly expressed in pancreatic cancer tissues with TP53 and KRAS mutations, respectively. However, the level of expression of PLOD3 in SMAD4 wild-type pancreatic cancer was increased. Conclusion: The findings showed that individual PLOD genes or PLOD family genes could be potential prognostic biomarkers for PAAD.