Yüksek Snail ekspresyonu Kolorektal Kanser Kökenli Karaciğer Metaztaslarında Rezeksiyon Sonrası Nüksü Yansıtır

Year 2022, , 672 - 679, 28.12.2022

Ahmet Karamustafaoğlu , Secil Ak Aksoy , Berrin Tunca , Melis Erçelik , Çağla Tekin , Nesrin Uğraş , Ömer Yerci , Fuat Aksoy , Ekrem Kaya

https://doi.org/10.31832/smj.1128434

Abstract

Amaç: Cerrahi tedavi, primer kolorektal kanserden (KRK) gelişen karaciğer metastazları için etkili tedavi yöntemlerinden biridir. Bununla birlikte metastazektomi sonrası nüks bu kanserlerdeki en büyük problemdir. Mevcut çalışmada, primer KRK’lardan gelişen karaciğer metastazlarında Epitelyal-Mezenkimal Tranzisyon (EMT)’nin metastazektomi sonrası nüks gelişimindeki rolünün incelenmesi amaçlanmıştır.
Gereç ve Yöntemler: Çalışmada, 85 hasta, 12 normal kolon, 8 normal karaciğer dokusu değerlendirildi. Hastalara ait arşiv materyali tümör ve normal dokularından RNA izolasyonları yapıldı. qRT-PCR kullanılarak 7 farklı EMT belirtecinin ekspresyon profili incelendi.
Bulgular: Seksen beş KRK’nın %24.7 (n=21)’sinde karaciğere metastazı gelişti. Karaciğer metastazı belirlenen hastaların %42.3’ünde (n=9) metastazektomi sonrası nüks gözlendi. Primer KRK’dan mKK gelişiminde EMT belirteçlerinden TWIST ve SNAIL ekspresyonlarında istatistiksel olarak anlamlı artış belirlendi (p<0.05). Cerrahi tedavi sonrası nüks eden mKK’larda ise EMT belirteçlerinden sadece SNAIL ekspresyonunda nüks etmeyen karaciğer dokularına göre nüks eden grupta istatistiksel olarak anlamlı artış gösterdi (p<0.0001).
Sonuç: Çalışma sonucunda, yüksek SNAIL ekspresyonuna sahip primer KRK tümörlerinin takip süresi içerisinde mKK geliştireceğini ve bu vakalara metastazektomi yapılmasına rağmen sonrasında nüks oluşabileceği öngörülmektedir.

Keywords

Metastazektomi, metastatik karaciğer kanserleri, Epitelyal-Mezenkimal Tranzisyon

Supporting Institution

Bursa Uludağ Üniversitesi Bilimsel Araştırmalar Projeler Birimi (BAP)

Project Number

KUAP(T)-2019/8

High SNAIL Expression Reflects Of Recurrence After Resection Colorectal Cancer Liver Metastasis

Abstract

Introduction: Metastasectomy is one of the effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). However, recurrence after metastasectomy is the biggest problem in these cancers.
The present study aimed to examine the role of Epithelial-Mesenchymal Transition (EMT) in the development of recurrence after metastasectomy in liver metastases from primary CRCs.
Materials and Methods: In the study, 85 patients were evaluated. RNA was isolated from archive tumors and normal tissues of the patients. Expression profiles of 7 different EMT markers were examined using qRT-PCR.
Results: Metastasis to the liver developed in 24.7% (n=21) of 85 CRC. Recurrence was observed in 42.3% (n=9) of liver metastases after metastasectomy. Statistically significant increases were detected in the expression of EMT markers TWIST and SNAIL in the development of mCC in primary CRC (p<0.05). On the other hand, in recurrent mCCs after metastasectomy, only SNAIL expression, one of the EMT markers, showed a statistically significant increase in the relapsed group compared to non-relapsed liver tissues (p<0.0001).
Conclusion: As a result of the study, it is predicted that primary CRC tumors with high SNAIL expression will develop mCC within the follow-up period, and recurrence may occur after metastasectomy in these cases.

Keywords

Metastasectomy, metastatic liver cancers, Epithelial-Mesenchymal Transition

Project Number

KUAP(T)-2019/8

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2020;70:7-30.
• 2. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics. CA Cancer J Clin. 2020;70:145-164.
• 3. Weiser MR, Jarnagin WR, Saltz LB. Colorectal cancer patients with oligometastatic liver disease: what is the optimal approach? Oncology. 2013;27(11):1074–8.
• 4. Gunawardene A, Desmond B, Shekouh A, Larsen P, Dennett E. Disease recurrence following surgery for colorectal cancer: five-year follow-up. N Z Med J. 2018;131(1469):51–8.
• 5. Segal NH, Saltz LB. Evolving treatment of advanced colon cancer. Annu Rev Med. 2009;60:207-219.
• 6. Nieto MA. Epithelial-mesenchymal transitions in development and disease: old views and new perspectives. Int J Dev Biol. 2009;53(8-10):1541-1547.
• 7. Ye X, Tam WL, Shibue T, Kaygusuz Y, Reınhardt F, Eaton EN, et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015;525(7568):256-260.
• 8. Lindner P, Paul S, Eckstein M, Hampel C, Muenzner JK, et al. EMT Transcription factor ZEB1 alters the epigenetic landscape of colorectal cancer cells. Cell Death Dis. 2020;11(2):147.
• 9. Li L, Liu J, Xue H, Li C, Liu Q, Zhou Y, et al. A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis. Oncogene. 2020;39(10):2125-2139.
• 10. Zhao P, Guo S, Tu Z, Di L, Zha X, Zhou H, et al. Grhl3 induces human epithelial tumor cell migration and invasion via downregulation of E-cadherin. Acta Biochim Biophys Sin (Shanghai). 2016;48(3):266-274.
• 11. Kourtidis A, Lu R, Pence LJ, Anastasiadis PZ. A central role for cadherin signaling in cancer. Exp Cell Res. 2017;358(1):78-85.
• 12. Christou N, Perraud A, Blondy S, Jauberteau MO, Battu S, Mathonnet M. E-cadherin: A potential biomarker of colorectal cancer prognosis. Oncol Lett. 2017;13(6):4571–4576.
• 13. Yan X, Yan L, Liu S, Shan Z, Tian Y, Jin Z. N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer. Molecular Medicine Reports. 2015;12(2):2999-3006.
• 14. Al Khatib AM, Mărgăritescu C, Taisescu O, Andreiana BC, Florescu MM, Ciurea RN. Immunoexpression of E-cadherin, Snail and Twist in colonic adenocarcinomas. Rom J Morphol Embryol. 2019;60(2):531-536.
• 15. Yook JI, Li XY, Ota I, Fearon ER, Weiss SJ. Wnt-dependent regulation of the E-cadherin repressor snail. J Biol Chem. 2005;280(12):11740-11748.
• 16. Aiello NM, Kang Y. Context-dependent EMT programs in cancer metastasis. J Exp Med. 2019;216(5):1016-1026.
• 17. Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A, et al. Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis. 2013;34(11):2548–2557.
• 18. Okada T, Suehiro Y, Ueno K, Mitomori S, Kaneko S, Nishioka M, et al. TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer. Genes, chromosomes cancer. 2010;49:452–462.
• 19. Mikulits W. Epithelial to mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5(8):1169–1179.
• 20. Liu L, Sun Q, Davis F, Mao J, Zhao H, Ma D. Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies. Burns Trauma. 2022;8:10:tkac011.
• 21. Zhao YL, Zhu RT, Sun YL. Epithelial-mesenchymal transition in liver fibrosis. Biomed Rep. 2016;4(3):269-274.