Nadhum ISMAİEL, Rozhgar MOHAMMED, Hazha HİDAYAT

Kolorektal kanser tanı belirteçleri olarak adipoq ve P53 gen ekspresyonları

Amaç: Kolorektal kanser Batı dünyasında çok sık karşılaşılan ve ölüm oranı yüksek bir hastalıktır. Genetik, epigenetik ve çevresel faktörler arasında, hasta spesifik bir interaksiyon vardır, dolayısı ile çok çeşitli ve komplekstir. Bu çalışmada P53 ve Adipoq genlerinin ekspresyon seviyelerinin, kolorektal kanser riski üzerine etkisini incelemeyi amaçladık. P53 geni tümör süpressör bir gen olup, bir transkripsiyon faktörü olan P53 proteinini kodlar, genomik stabilitenin devamlılığında çok önemlidir. Adipoq geni adiponektini kodlar.Gereç ve Yönetim: Otuz iki kolorektal kanserli hastanın, tümör ve normal dokusundan RNA izolasyonu yapıldı. P53 ve Adipoq mRNA ekspresyon seviyeleri semi-quantitative reverse transkripsiyon-polimeraz zincir reaksiyonu (RT-PCR) yöntemi ile belirlendi.Bulgular: Kolorektal kanserde, P53 ekspresyon seviyesinin normal dokuya göre önemli oranda artış gösterdiği tesbit edilmiştir (aşırı ekspresyon). Fakat, Adipoq ekspresyon seviyesinin, kolorektal kanserinde normal dokuya oranla önemli derecede azaldığı belirlenmiştir (azalmış ekspresyon).Sonuç: Yaptığımız bu çalışmada elde ettiğimiz veriler, Adipoq gen ekspresyonu seviyesinin azaldığı, P53 geni ekspresyon seviyesinin ise artış gösterdiğine dair olup, bu genlerin kolorektal kanserli hastalarda teşhis markırı olarak kullanılabileceğini önermektedir. Kolorektal kanser ve teşhis biyomarkırları arasındaki ilişkiyi anlamak için, daha fazla çalışma yapılması gerekir.

Anahtar Kelimeler:

Kolorektal kanser, P53, adipoq

Gene expression of P53 and adipoq as diagnostic markers for colorectal cancer

Purpose: Colorectal cancer is the most frequent cause of death and had high mortality rate in Western world. It is from complex, variable and patient- specific interaction between genetic, epigenetic and environmental factors. In the present study, we aimed to investigate the contribution of gene expression of the P53 and Adipoq, both genes to the risk of colorectal cancer. P53 gene is a tumor suppressor gene, encoded protein of P53 is a transcription factor and its pivotal role in maintaining genomic stability. Adipoq gene codes adiponectin.Material and Methods: Total RNA were extracted from paired tumor and normal tissues of 32 colorectal cancer patients. The mRNA expression level of P53 and Adipoq were measured employing semi- quantitative reverse transcription- polymerase chain reaction (RT- PCR). Results: The mRNA expression level of P53 in colorectal cancer was significantly increased according to normal samples (over-expressed). However, the mRNA expression level of Adipoq in colorectal cancer was significantly reduced according to normal samples (down- regulated).Conclusion: In current study, our data suggest those reduced mRNA expression of the Adipoq and increased mRNA expression of P53 might be useful molecular diagnostic markers for colorectal cancer patients. In order to understand the investigation between colorectal cancer and diagnostic biomarker; further analysis is necessary.

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Chuncui Y, Jun W, Shiyun T, Jun Z, Ming L, Peng S. Meta-analysis of adiponectin polymorphisms and colorectal cancer risk. Int J Med Sci. 2013;10:1113- 20.
Al-Sohaily S, Biankin A, Leong R, Kohonen M, Warusavitarne J. Molecular pathways in colorectal cancer. J Gastroenterol Hepatol. 2012;27:1423-31.
Taib JST, İğci M, Borazan E, Bayraktar E, Balık A, Çakmak EA et al. Investigation of MACC1-AS1 gene mutations in colorectal cancer. Gaziantep Med J. 2014;20:174-81.
Gingras D, Béliveau R. Colorectal cancer prevention through dietary and lifestyle modifications. Cancer Microenviron. 2011;4:133-9.
Risch N. The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiol Biomarkers Prev. 2001;10:733-41. 6. EGFR Gene. http://www.genecards.org/cgi-bin/ gene = Adipoq and P53. (Protein coding) carddisp.pl?
Matsuzawa Y. Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2006;3:35- 42..
Mahmoud N, Nourkhoda S, Hamid A, Khosrow E. Inflammatory markers and adipocytokine responses to exercise training and detraining in men who are obese. J Strength Cond Res. 2014;28:3399-3410.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K et al. . The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941-6.
Cnop M, Havel PJ, Utzschneider KM. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003;4:459-69.
Yang WS, Chuang LM. Human genetics of adiponectin in the metabolic syndrome. J Mol Med. 2006;84:112-21.
George P. P53 How crucial is its role in cancer?. Int J Curr Pharm Res. 2011;3:19- 25.
Cassidy J, Bisset D, Spence RA, Payne A. Oncology. 2nd ed. New York, Oxford, 2006.
Liu Y, Bodmer W. Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines. PNAS. 2006;103:976-81.
Nejad A, Yaghoobi M. Mutation analysis of TP53 tumor suppressor gene in colorectal cancer in patients from Iran (Kerman Province). Iran J Basic Med Sci. 2012;15:683-90.
Bayraktar E, Igci M, Erturhan S, Igci YZ, Karakok M, Gogebakan B et al. Reduced gene expression of Bikunin as a prognostic marker for renal cell carcinoma. Exp Oncol. 2014;36:107-11.
Khailany RA, Igci M, Bayraktar E, Erturhan S, Karakok M, Arslan A. VHL, PBRM1 and SETD2 genes in kidney cancer: a molecular investigation. International Journal of Medical, Health, Biomedical and Pharmaceutical Engineering. 2015;9:389-92.
Bilbao A, Armañanzas R, Ispizua Z, Calvo B, Varona A, Inza I et al. Identification of a biomarker panel for colorectal cancer diagnosis. BMC Cancer. 2012;12:1- 13.
Yamamoto N, Oshima T, Yoshihara K, Sato T, Yamada R, Fujii S et al. Reduced expression of the AdipoR1 gene is correlated with venous invasion in colorectal cancer. Mol Med Rep. 2009;2:555-9.
El-Mahdani N, Vaillant JC, Guiguet M, Prevot S, Bertrand V, Bernard C et al. Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation. Br J Cancer. 1997;75:528-36.
George E, Karafoka E, Joanna G, Stamopoulos P, Constantinos P, Bramis K et al. p53 and EGFR expression in colorectal cancer: a reappraisal of ‘old’ tissue markers in patients with long follow-up. Anticancer Res. 2009;29:785-92.
Goel A, Boland C. Epigenetics of colorectal cancer. Gastroenterology. 2012;143:1442-60 .