Moreover, GAPDH expression is regulated by transcription factors which are frequently altered in cancer such as HIF-1α, p53 or AP-1. In fact, GAPDH is one of the multifaceted glycolytic enzymes that contributes to cell survival and resistance to cell death, becoming a promising biomarker in cancer research. GAPDH is constituted by four identical subunits of 37 kDa and has binding sequences for coenzymes NAD+ and NADH and for nucleic acids. GAPDH catalyses the phosphorylation and oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate coupled with the reduction of NAD+ to NADH. This fact advises against its widely extended use as a housekeeping gene. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) is an essential regulator of glycolysis ubiquitously overexpressed in 21 cancer classes, being one of the three glycolytic genes overexpressed in colorectal cancer, along with enolase and pyruvate kinase. However, further studies are required to identify new biomarkers to predict CRC outcome, help to understand its evolution and find the most suitable treatment. Cancer staging systems help oncologists to evaluate disease prognosis, treatment suitability and the possibilities of patients to be enrolled in specific clinical trials, contributing to fight CRC. The American Joint Committee on Cancer (AJCC) TNM staging system establishes four different stages of tumour progression (I to IV) depending on the primary tumour extent (T), the regional lymph node involvement (N) and the absence or presence of distant metastasis (M). Fortunately, systematic risk population screening programmes facilitate early detection and treatment reducing its incidence and mortality rate. In addition, cancer cells from the primary site can have the ability to invade other tissues resulting in metastasis, the major cause of death from cancer.Ĭolorectal cancer (CRC) is a global leading cause of cancer-related mortality being the third most common cancer in men and the second in women worldwide. Cancer is a prevalent multifactorial disease characterised by loss of physiological control and malignant transformation of cells that acquire functional and genetic abnormalities, leading to tumour development and progression. Multifactorial diseases result from the interaction between genetic susceptibility and environmental factors and do not exhibit a clear hereditary pattern, which causes difficulties in their risk evaluation, diagnosis and treatment. Studying the role of GAPDH in malignant transformation can shed new light on the understanding of tumour onset and lead to the design of more efficient personalised therapies. These results were reinforced by those obtained at mRNA level. Overexpression of GAPDH is positively associated with early stage tumours without regional lymph node and distant metastases involved. Groups were compared using Kruskal-Wallis tests. Probability of patient survival and disease-free survival were analysed by the univariate product-limit method of Kaplan-Meier. Gene expression profiling was performed using Affymetrix microarrays. Staining quantification was performed by computational image analysis, and correlations between GAPDH expression and tumour progression stage were assessed. GAPDH expression was immunohistochemically analysed in tumour tissues from 62 colorectal cancer (CRC) patients, and validated at mRNA level in an independent dataset comprising 98 paired stage II CRC and normal samples. Given the pivotal role of GAPDH in tumour metabolism, our aim was to correlate its protein expression with tumour staging and prognosis of colorectal cancer. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential regulator of glycolysis used as a housekeeping marker for gene/protein normalisation.
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