The role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 in esophageal squamous cell carcinoma

Abstract

6-phosphofructo-kinase-2/fructose diphosphatase-2 isoenzyme 3 (PFKFB3) is closely related to the growth of many types of cancer cells. Glycolysis not only provides Adenosine triphosphate for the growth of tumor cells, but also protects them from acid products, which is beneficial to the invasion and metastasis of tumors. However, PFKFB3 expression in esophageal squamous cell carcinoma (ESCC) has been scarcely reported. In this study, the role of PFKFB3 was studied in 120 ESCC samples using immunohistochemistry technique (IHC), western blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR). Both PFKFB3 protein and gene expression in ESCC tissues were significantly higher than in adjacent non-tumor tissues (P < .05). Single factor analysis showed that both PFKFB3 protein and gene expression are related to infiltration depth, stage, tumor metastasis, and the degree of tumor differentiation in ESCC. Multifactor Cox survival analysis revealed that PFKFB3 protein expression, tumor location, tumor metastasis, tumor differentiation degree, and tumor stage were independent factors affecting the overall survival of postoperative patients. Multivariate Cox survival analysis showed that PFKFB3 mRNA has a good performance for predicting 3-year survival of patients with ESCC 0.89 (0.79–0.99), with a sensitivity of 0.85 and specificity of 0.77. Encouragingly, the sensitivity and specificity of PFKFB3 in the diagnosis of early ESCC (stage I and stage II) can reach 87.8% and 91.5%. In conclusion, high PFKFB3 protein and gene expression may be associated with the occurrence, development, and prognosis of ESCC. PFKFB3 could be used to help develop new therapeutic and diagnostic strategies for ESCC patients.

Noncoding RNA-Mediated High Expression of PFKFB3 Correlates with Poor Prognosis and Tumor Immune Infiltration of Lung Adenocarcinoma

“…Understanding its mechanism of occurrence and development may provide new methods and ideas for the treatment of LUAD; therefore, seeking new molecular prognostic markers is essential. There is growing evidence demonstrating that PFKFB3 plays an important role in promoting tumor progression in different kinds of human cancers, 21 such as ESCC, 22 LUAD. In addition, in our previous study, we have found that PFKFB3 is an oncogene in LUAD tumor progression and concluded that targeting PFKFB3 may become a promising therapy, 23 however, fewer samples were collected, and the clinical value was not analyzed.…”

An energy metabolism-based eight-gene signature correlates with the clinical outcome of esophagus carcinoma

“…Multiple genes have been implicated in the regulation of cell energy metabolism process in ESC [5,6,12,25,26]. In particular, several EMRGs, such as RAC1 [5], TKTL1 [27], and PFKFB3 [28] were shown to be associated with prognosis in patients with ESC. However, previous studies were limited by just single gene detected, small sample sizes, and lack of independent validation.…”