The Value of Expression of M2-PK and VEGF in Patients with Advanced Gastric Cancer

Abstract

Glycolytic pyruvate kinase isoenzyme type M2 (M2-PK) plays a key role in tumor metabolism and energy production. Vascular endothelial growth factor (VEGF) is critical in regulating angiogenesis which is an essential process required for tumor growth and metastasis. These two genes may function in accordance with tumor development. The purpose of this study was to investigate the relationship between the expression of M2-PK and VEGF, and their association with clinicopathological features in patients with advanced gastric cancer. Expression of M2-PK and VEGF were examined in 142 cases of paraffin-embedded tissue blocks from patients with advanced gastric cancer. M2-PK expression was found to strongly correlate with that of VEGF (r = 0.718). In addition, expression of M2-PK and VEGF correlates with tumor size (p = 0.0001, and p = 0.0017, respectively), depth of invasion (p = 0.0024, and p = 0.0261, respectively), and lymph node metastasis (p = 0.036, and p = 0.028, respectively). The high expression levels of M2-PK and VEGF may indicate poor prognosis in patients with advanced gastric cancer.

Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer

“…Previous findings have indicated that PKM2 and LDH5 are commonly overexpressed in a broad spectrum of cancers and are required for tumour metabolism and growth. Overexpression of PKM2 or LDH5 was associated significantly with adverse clinicopathological features, including advanced tumour stage, lymph node metastasis and unfavourable prognosis in diverse cancers including head and neck squamous cell carcinoma . Consistent with these previous findings, our data from tongue cancerous cell lines indicated that PKM2 and LDH5 protein were both up‐regulated significantly compared with non‐tumorigenic oral epithelial cells.…”

“…Until now, several clinicopathological prognostic indicators have been proposed, including clinical stage, histological grade and cervical node metastasis . Previous findings have suggested that PKM2 and LDH5 expression are of prognostic significance in a variety of malignancies . Our results indicate clearly that high PKM2 or LDH5 expression associates significantly with decreased overall patient survival.…”

“…LDHA, and in particular the LDH5 tetramer, is the predominant and efficient isoform found in highly glycolytic tissues, especially cancers . Importantly, widespread overexpression of PKM2 and LDHA/5 has been observed in multiple human cancers, including gastric, breast and head and neck cancer . Their up‐regulation correlates significantly with aggressive behaviour, clinicopathological features, therapeutic resistance and unfavourable treatment outcomes.…”

“…11 Importantly, widespread overexpression of PKM2 and LDHA/5 has been observed in multiple human cancers, including gastric, breast and head and neck cancer. [12][13][14][15] Their upregulation correlates significantly with aggressive behaviour, clinicopathological features, therapeutic resistance and unfavourable treatment outcomes. Further evidence linking PKM2 and LDHA/5 to tumorigenesis comes from previous findings that PKM2 and LDHA are the direct targets of several well-established oncogenic pathways, including HIF-1, Myc and PI3K-Akt-mTOR.…”

Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

“…6,7 This findings have been supported by the facts that abnormal overexpression of PKM2 has been frequently observed in multiple human cancers and its upregulation correlates with cancer aggressive behaviors and clinicopathological features, therapeutic resistance and unfavorable treatment outcomes. [8][9][10] Further evidence linking PKM2 to tumorigenesis also comes from previous findings that PKM2 depletion via either RNA interference or pharmacologic agents impaired cancer cell proliferation, induced cell apoptosis, enhanced therapeutic sensitivity and decreased tumorigenicity both in vitro and in vivo. [11][12][13] Collectively, these findings have provided proof-of-principle that PKM2 is the bona fide oncogene mediating cancer metabolic reprogramming as well as an attractive therapeutic target.…”