title: Identification of the TP53-induced glycolysis and apoptosis regulator in various stages of colorectal cancer patients.
abstract: The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (p<0.01) and stage III (p<0.05) when compared to adjacent normal tissue. Immunohistochemical studies revealed that TIGAR expression was increased in colorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (p<0.05) and late stage (stage III and IV) CRC (p<0.01). TIGAR protein was also found to be highly expressed in stage II and III colorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer.
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Khayal
authors.initials: K
authors.lastname: Al-Khayal
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Maha
authors.initials: M
authors.lastname: Abdulla
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Obeed
authors.affiliation: Department of Surgery, College of Medicine, Al-Faisal University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Wael
authors.initials: W
authors.lastname: Al Kattan
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zubaidi
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Mansoor-Ali
authors.initials: MA
authors.lastname: Vaali-Mohammed
authors.affiliation: Department of Pathology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdulmalik
authors.initials: A
authors.lastname: Alsheikh
authors.affiliation: Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Rehan
authors.initials: R
authors.lastname: Ahmad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010744:Phosphoric Monoester Hydrolases; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human