Otofajinin kolorektal kanserde önemi: Kesitsel bir çalışma

Year 2019, , 246 - 249, 15.03.2019

Hilmi Erdem Sümbül , Hikmet Akkız

https://doi.org/10.28982/josam.536733

Cited By: 1

Abstract

Amaç: Kolon kanseri tüm dünyada kadınlar ve erkeklerde üçüncü en sık gözlenen kanserdir. Yılda yaklaşık 1.200.000 yeni vaka ve yaklaşık 609.000 ölüm tahmin edilmektedir. Erkek ve kadınlardaki kanserlerin yaklaşık %10’unu oluşturmaktadır. Otofaji, hücresel proteinlerin otofajik vakuoller aracılığı ile lizozomal degredasyonudur. Otofaji gelişimde, uzun yaşamda ve kanser gibi pek çok hastalığın patogenezinde büyük rol oynamaktadır. Tümör gelişimi ve uyarılması üzerine bazı etkiler gösterdiği saptanmıştır. Bu çalışmanın amacı, otofajinin, otofaji ilişkili ATG5, ATG12 ve Beclin-1genlerinin ve proteinlerinin ekspresyonu ve kolorektal kanserin klinikopatolojik özellikleri ile ilişkisinin belirlenmesidir. 

Yöntemler: Çukurova Üniversitesi Tıp Fakültesi Hastanesi Genel Cerrahi Anabilim Dalında kolorektal kanser nedeniyle opere edilen 45 hasta dahil edildi. Hastaların hem tümör hem de eşlenik normal kolon dokularından alınan örnekler ameliyathaneden itibaren sıvı azotta bankalandı. Daha sonra SYBR Green qPCR yötemiyle ATG5, ATG12, Beclin-1 gen ekspresyonlarına ve Western Blot yöntemiyle ATG5, Beclin-1, LC3 protein ekspresyonlarına bakıldı. Ekspresyon düzeyleri ile klinikopatolojik özellikler karşılaştırıldı.

Bulgular: Gen ve protein ekspresyonları hem tümör hem de eşlenik normal doku örneklerinin çoğunda saptandı. Gen ekspresyon düzeyleriyle klinikopatolojik ve demografik veriler arasında anlamlı ilişki saptanamadı. Örneklerin TNM evreleriyle perinöral invazyon ve lenfovasküler invazyon arasında anlamlı ilişki saptandı.

Sonuç: Bu çalışmanın sonuçları otofajinin kolorektal karsinogenezisde işe karıştığını önermektedir. Genişletilmiş çalışmaların yapılması otofaji ve kolorektal kanser ile ilişkili klinikopatolojik özellikleri belirlemede faydalı olabilecektir.

Keywords

ATG, Otofaji, Kolorektal kanser

Importance of autophagy in colorectal cancer: A cross-sectional study

Abstract

Aim: Colon cancer is the third most common cancer in women and men all over the world. Colorectal cancer (CRC) is diagnosed in over 1.2 million people globally each year. The disease is responsible for approximately 609,000 deaths a year (10% of all cancer cases in women and men). Autophagy is the basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components through the actions of lysosomes. The development of autophagy plays a great role in the pathogenesis of many diseases. It was found that autophagy could influence on tumor progression and stimulation. The purpose of this study is to determine the relationship between autophagy and autophagy related ATG5, ATG12, Beclin-1 gene and protein expressions and clinicopathological features of colorectal cancer.

Methods: An observational study is planned. After approval of the ethical committee, the patients (n=45) operated for colorectal cancer was included to the study. There were totally 90 tissue samples taken and banked in liquid nitrogen: 1 tissue sample from tumor and 1 from normal from each patient. ATG5, ATG12, Beclin-1 gene expression levels in all samples were examined using SYBR- Green qPCR method, and, ATG5, Beclin-1, LC3 protein levels were analyzed using Western blotting technique. Expression levels were compared to clinicopathologic characteristics.

Results: Gene and protein expression in both tumor and normal tissue equivalents were studied in most of the examples. There was no significant correlation between gene expression levels and demographic or clinicopathological features. The TNM stage of cases significantly correlated with perineural invasion and lymphovascular invasion.

Conclusion: The results of this study suggest that autophagy may play a role in carcinogenesis of colorectal cancers. The further studies are required to determine the relationship between autophagy and clinicopathologic features associated with colorectal cancers.

Keywords

ATG, Autophagy, Colorectal cancer

References

• 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277-300.
• 2. Miller BA, Chu KC, Hankey BF, Ries LA. Cancer incidence and mortality patterns among specific Asian and Pacific Islander populations in the U.S. Cancer Causes Control. 2008;19(3):227-56.
• 3. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-36.
• 4. Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF, Gigot JF, et al. Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008;26(29):4828-33.
• 5. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22(2):229-37.
• 6. Prenen H, Vecchione L, Van Cutsem E. Role of targeted agents in metastatic colorectal cancer. Target Oncol. 2013;8(2):83-96.
• 7. Melet A, Song K, Bucur O, Jagani Z, Grassian AR, Khosravi-Far R. Apoptotic pathways in tumor progression and therapy. Adv Exp Med Biol. 2008;615:47-79.
• 8. Eisenberg-Lerner A, Kimchi A. The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis. 2009;14(4):376-91.
• 9. Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Kim SS, et al. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol. 2009;217(5):702-6.
• 10. Kim MS, Song SY, Lee JY, Yoo NJ, Lee SH. Expressional and mutational analyses of ATG5 gene in prostate cancers. APMIS. 2011;119(11):802-7.
• 11. Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007;17(10):839-49.
• 12. Baehrecke EH. Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol. 2005;6(6):505-10.
• 13. Hannigan AM, Gorski SM. Macroautophagy: the key ingredient to a healthy diet? Autophagy. 2009;5(2):140-51.
• 14. LoRusso PM. Mammalian target of rapamycin as a rational therapeutic target for breast cancer treatment. Oncology. 2013;84(1):43-56.
• 15. Knaevelsrud H, Ahlquist T, Merok MA, Nesbakken A, Stenmark H, Lothe RA, et al. UVRAG mutations associated with microsatellite unstable colon cancer do not affect autophagy. Autophagy. 2010;6(7):863-70.
• 16. Furuya N, Yu J, Byfield M, Pattingre S, Levine B. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy. 2005;1(1):46-52.
• 17. Akar U, Chaves-Reyez A, Barria M, Tari A, Sanguino A, Kondo Y, et al. Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy. 2008;4(5):669-79.
• 18. Hippert MM, O'Toole PS, Thorburn A. Autophagy in cancer: good, bad, or both? Cancer Res. 2006;66(19):9349-51.
• 19. Wei H, Guan JL. Pro-tumorigenic function of autophagy in mammary oncogenesis. Autophagy. 2012;8(1):129-31.
• 20. Gong C, Bauvy C, Tonelli G, Yue W, Delomenie C, Nicolas V, et al. Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Oncogene. 2013;32(18):2261-72,72e 1-11.
• 21. Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5(11):876-85.
• 22. Gozuacik D, Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004;23(16):2891-906.
• 23. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, et al. A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 2001;61(2):439-44.
• 24. Al-Sohaily S, Biankin A, Leong R, Kohonen-Corish M, Warusavitarne J. Molecular pathways in colorectal cancer. J Gastroenterol Hepatol. 2012;27(9):1423-31.