Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential. However, no good biomarker has been identified to refine which subtype is of high metastatic potential to make decisions regarding the elective and therapeutic management of lymphatic metastases. In this study, we investigated the role of the metabolic enzyme phosphoglycerate mutase 1 (PGAM1) in OSCC. PGAM1 expression was examined in tissue samples of 122 OSCC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazards model. Moreover, PGAM1 was knocked down in the OSCC cell lines Cal27 and HN12, followed by determination of the change in cell migration and signaling pathways. PGAM1 expression is correlated with age, lymphatic metastasis and tumor recurrence and is closely associated with poor overall survival (OS) and disease-free survival (DFS). Intriguingly, PGAM1 is an independent risk factor for OS and DFS. After knocking down PGAM1 in Cal27 and HN12 cells, cell migration was remarkably decreased along with signaling pathway molecules, such as proto-oncogene c-SRC (SRC), Focal adhesion kinase (FAK) and Paxillin. The effect on cell migration was abolished following pretreatment with an SRC inhibitor. This study suggested that PGAM1 is a poor prognostic biomarker of OSCC and may be used to select patients of high metastatic potential in the clinic, and PGAM1 promotes the migration of OSCC cells is associated with the SRC pathway.

Identification of Proteomic Markers in Head and Neck Cancer Using MALDI–MS Imaging, LC–MS/MS, and Immunohistochemistry

“…Inhibiting PGAM1 activity induces reduced tumor growth and decreased apoptosis. Additionally, it is suggested as a poor prognostic marker in OSCC . Our detection of PGAM1 supports its role as potential marker for tumor growth.…”

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy

“…PGAM1 was reported to be highly expressed in 65 (53%) of the samples and this expression was associated with tumor recurrence and lymphatic metastasis. High expression of PGAM1 was closely linked to the poor overall survival with 1.579 versus 7.440 survival rate in low versus high expression of PGAM1 respectively . All these findings provide a baseline that PGAM1 might serve as novel prognostic biomarker for cancer.…”

“…High expression of PGAM1 was closely linked to the poor overall survival with 1.579 versus 7.440 survival rate in low versus high expression of PGAM1 respectively. 31 All these findings provide a baseline that PGAM1 might serve as novel prognostic biomarker for cancer.…”

“…Foregoing investigations have revealed PGAM1 overexpression in several cancers such as clear cell renal carcinoma (CCRC), glioma, oral squamous cell carcinoma (OSCC), breast cancer, human nonsmall lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, hepatocellular carcinoma, and urothelial bladder cancer ( Table and Figure ).…”

“…27 Thus, PGAM1 has potential ability to derive the metastasis in a metabolic independent way. 31 breast cancer, 32 human nonsmall lung cancer, 33 pancreatic ductal adenocarcinoma, 34 prostate cancer, 35 colorectal cancer, 36 hepatocellular carcinoma, 14 and urothelial bladder cancer 37 ( Table 2 and Figure 3). In the hypoxia tumor microenvironment, cancer cells are oxygen independent for energy production.…”