Retrospective Study
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World J Gastroenterol. Dec 28, 2014; 20(48): 18390-18396
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18390
Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages
Omar A Al Obeed, Khayal A Alkhayal, Abdulmalik Al Sheikh, Ahmad M Zubaidi, Mansoor-Ali Vaali-Mohammed, Robin Boushey, James H Mckerrow, Maha-Hamadien Abdulla
Omar A Al Obeed, Khayal A Alkhayal, Ahmad M Zubaidi, Mansoor-Ali Vaali-Mohammed, Maha-Hamadien Abdulla, Colorectal Research Center, Department of Surgery, King Saud University, Riyadh 11472, Saudi Arabia
Abdulmalik Al Sheikh, Department of Pathology, King Saud University, Riyadh 11472, Saudi Arabia
Robin Boushey, Division of General Surgery, Ottawa Hospital, University of Ottawa, Ontario K1H 8L6, Canada
James H Mckerrow, Maha-Hamadien Abdulla, Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, CA 94158-2330, United States
Author contributions: Al Obeed OA contributed to data collection, design of experiments and writing of manuscript; Alkhayal KA and Zubaidi AM contributed to data collection and data analysis; Vaali-Mohammed MA contributed to conduction of experiments and data analysis; Al Sheikh A contributed to construction of tissue microarray and review of patients’ histopathology; Boushey R contributed to design of experiments and writing of manuscript; Mckerrow JH contributed to design of experiments, writing of manuscript, evaluation of histological sections and tissue microarray; and Abdulla MH contributed to design the experiments, conducted the experiments, tissue microarray planning, and writing of manuscript.
Correspondence to: Maha-Hamadien Abdulla, PhD, Assistant Professor, Director of Colorectal Research Center, Department of Surgery, King Khalid University Hospital, King Saud University, PO Box 7805(37), Riyadh 11472, Saudi Arabia. mabdulla@ksu.edu.sa
Telephone: +966-1- 4671575 Fax: + 9661-4692728
Received: November 7, 2013
Revised: February 23, 2014
Accepted: June 20, 2014
Published online: December 28, 2014
Abstract

AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer.

METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry.

RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor.

CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

Keywords: Tumor necrosis factor-α, Colorectal cancer, Real time polymerase chain reaction, Immunohistochemistry, mRNA

Core tip: The relative expression of tumor necrosis factor-α (TNF-α) mRNA in colorectal cancer tumor tissue was significantly higher than adjacent normal tissue. In addition, higher TNF-α gene expression was associated significantly with advanced tumor as compared to early tumor stages. Colorectal tumor tissue contained many TNF-α positive cells, whereas normal colorectal tissue contained very few positive cells. We showed elevated TNF-α gene expression by cancer cells, which correlated strongly with advanced tumor stages. High levels of TNF-α expression could be an independent prognostic indicator, and targeting TNF-α may be a promising tool, which can be used to follow-up patients with colorectal carcinoma.