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Prognostic Significance of Notch-4, SATB-2, and Glutaminase-1 in Colorectal Adenocarcinoma

Document Type : Original Article(s)

Authors

1 Pathology Department, Medicine College, Zagazig University, Egypt

2 Department of Clinical Oncology and Nuclear Medicine, Medicine College, Zagazig University, Egypt

Abstract

Background: Neurogenic locus notch homology 4 (Notch-4) is crucial in maintaining stem cells. Special AT-rich sequence-binding protein 2 (SATB-2) is a transcription factor that binds to the nuclear matrix and serves various functions, including brain development. Glutaminase-1 (GLS-1) plays a pivotal role in cancer cell metabolism, growth, and proliferation. This study aims to assess the expression of these markers in colorectal cancer, establishing correlations with clinicopathological characteristics and patient survival.
Method: In this retrospective study, we retrieved and analyzed 68 formalin-fixed, paraffin-embedded blocks of primary colorectal adenocarcinoma, not otherwise specified cases, and adjacent normal mucosa. Notch-4, SATB-2 and GLS-1 expressions were analyzed using immunohistochemistry at the Zagazig School of Medicine, Egypt.
Results: High expressions of Notch-4 and GLS-1 and low expression of SATB-2 were observed in colonic adenocarcinoma but not in adjacent non-neoplastic mucosa (P < 0.001). High expressions of Notch-4 and GLS-1, along with low expression of SATB-2, were associated with a higher tumor grade, advanced stage (P < 0.001), lymphovascular invasion, lymph node metastasis, and poor disease-free survival and overall survival rates (P < 0.001).
Conclusion: High expression of Notch-4 and GLS-1 is correlated with a poor prognosis in colorectal cancer, while high expression of SATB-2 is associated with a favorable prognosis for colorectal carcinoma. These markers can aid in predicting tumor prognosis and guiding targeted therapy for colorectal carcinoma.

Highlights

Noha F. Elaidy (PubMed)

Mohamed W. Hegazy (PubMed)

Keywords

Main Subjects

How to cite this article:

Elaidy NF, Elwan A, Hegazy MW, Atwa HA. Prognostic significance of Notch-4, SATB-2, and glutaminase-1 in colorectal adenocarcinoma. Middle East J Cancer. 2024; 15(1):15-24. doi: 10.30476/mejc.2023.97207.1852.

References
  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin. 2020;70(4):313.
  2. Gado A, Ebeid B, Abdelmohsen A, Axon A. Colorectal cancer in Egypt is commoner in young people: is this cause for alarm? Alex J Med. 2014;50(3):197–201. doi: 10.1016/j.ajme.2013.03.003.
  3. Aran V, Victorino AP, Thuler LC, Ferreira CG. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer. 2016;15(3):195-203. doi: 10.1016/j.clcc.2016.02.008.
  4. Annett S, Robson T. Targeting cancer stem cells in the clinic: Current status and perspectives. Pharmacol Ther. 2018; 187:13-30. doi: 10.1016/j.pharmthera.2018.02.001.
  5. Aster JC, Pear WS, Blacklow SC. The varied roles of Notch in cancer. Annu Rev Pathol. 2017;12:245-75. doi: 10.1146/annurev-pathol-052016-100127.
  6. Nowell CS, Radtke F. Notch as a tumour suppressor. Nat Rev Cancer. 2017;17(3):145-159. doi: 10.1038/nrc.2016.145.
  7. Berg KB, Schaeffer DF. SATB2 as an immunohistochemical marker for colorectal adenocarcinoma a concise review of benefits and pitfalls. Arch Pathol Lab Med. 2017;141(10):1428–33. doi: 10.5858/arpa.2016-0243-RS.
  8. Hrudka J, Matěj R, Nikov A, Tomyak I, Fišerová H, Jelínková K, et al. Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer. Sci Rep. 2022;12(1):19152. doi: 10.1038/s41598-022-22685-0.
  9. Guo C, Xiong D, Yao X, Gu W, Zhang H, Yang B, et al. Decreased SATB2 expression is associated with metastasis and poor prognosis in human clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2015;8(4):3710-8.
  10. Ma C, Olevian DC, Lowenthal BM, Jayachandran P, Kozak MM, Chang DT, et al. Loss of SATB2 expression in colorectal carcinoma is associated with DNA mismatch repair protein deficiency and BRAF mutation. Am J Surg Pathol. 2018;42(10):1409-17. doi: 10.1097/PAS.0000000000001116.
  11. Dum D, Kromm D, Lennartz M, De Wispelaere N, Büscheck F, Luebke AM, et al. SATB2 expression in human tumors. Arch Pathol Lab Med. 2023;147(4):451-64.doi:10.5858/arpa.2021-0317-OA.
  12. Zhang J, Pavlova NN, Thompson CB. Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine. EMBO J. 2017;36(10):1302-15. doi: 10.15252/embj.201696151.
  13. Tanaka K, Sasayama T, Irino Y, Takata K, Nagashima H, Satoh N, et al. Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest. 2015;125(4):1591-602. doi: 10.1172/JCI78239.
  14. Pan T, Gao L, Wu G, Shen G, Xie S, Wen H, et al. Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer. Biochem Biophys Res Commun. 2015; 456(1):452-8. doi: 10.1016/j.bbrc.2014.11.105.
  15. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014;13(4): 890-901. doi: 10.1158/1535-7163.MCT-13-0870.
  16. Zhang Z, Bu X, Yang J, Zhu S, He S, Zheng J, et al. NOTCH4 regulates colorectal cancer proliferation, invasiveness, and determines clinical outcome of patients. J Cell Physiol. 2018;233(10):6975-85. doi: 10.1002/jcp.26619.
  17. Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, et al. Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Arch Pathol Lab Med. 2014; 138(8):1015-26. doi: 10.5858/arpa.2013-0452-OA.
  18. Xu L, Zhou D, Li F, Ji L. Glutaminase 2 functions as a tumor suppressor gene in gastric cancer. Transl Cancer Res. 2020;9(8):4906-13. doi: 10.21037/tcr-20-2246.
  19. Bonyadi Rad E, Hammerlindl H, Wels C, Popper U, Ravindran Menon D, Breiteneder H, et al. Notch4 signaling induces a mesenchymal-epithelial-like transition in melanoma cells to suppress malignant behaviors. Cancer Res. 2016;76(7):1690-7. doi: 10.1158/0008-5472.CAN-15-1722.
  20. Wu G, Chen Z, Li J, Ye F, Chen G, Fan Q, et al. NOTCH4 Is a Novel prognostic marker that correlates with colorectal cancer progression and prognosis. J Cancer. 2018;9(13):2374-9. doi: 10.7150/jca.26359.
  21. Fukusumi T, Guo TW, Sakai A, Ando M, Ren S, Haft S, et al. The NOTCH4-HEY1 pathway induces epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Clin Cancer Res. 2018;24(3):619-33. doi: 10.1158/1078-0432.CCR-17-1366.
  22. Mansour MA, Hyodo T, Ito S, Kurita K, Kokuryo T, Uehara K, et al. SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling. FEBS J. 2015;282(8):1394-405. doi: 10.1111/febs.13227.
  23. Dragomir A, de Wit M, Johansson C, Uhlen M, Pontén F. The role of SATB2 as a diagnostic marker for tumors of colorectal origin: Results of a pathology-based clinical prospective study. Am J Clin Pathol. 2014;141(5):630-8. doi: 10.1309/AJCPWW2URZ9JKQJU.
  24. Zhang YJ, Chen JW, He XS, Zhang HZ, Ling YH, Wen JH, et al. SATB2 is a promising biomarker for identifying a colorectal origin for liver metastatic adenocarcinomas. EBioMedicine. 2018;28:62-9. doi: 10.1016/j.ebiom.2018.01.001.
  25. Mezheyeuski A, Ponten F, Edqvist PH, Sundström M, Thunberg U, Qvortrup C, et al. Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study. Acta Oncol. 2020;59(3):284-90. doi: 10.1080/0284186X.2019.1691258.
  26. Luo LJ, Yang F, Ding JJ, Yan DL, Wang DD, Yang SJ, et al. MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. Gene. 2016;594(1):47-58. doi: 10.1016/j.gene.2016.08.057.
  27. Yang MH, Yu J, Chen N, Wang XY, Liu XY, Wang S, et al. Elevated microRNA-31 expression regulates colorectal cancer progression by repressing its target gene SATB2. PLoS One. 2013;8(12):e85353. doi: 10.1371/journal.pone.0085353.
  28. Xiang L, Mou J, Shao B, Wei Y, Liang H, Takano N, et al. Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization. Cell Death Dis. 2019;10(2):40. doi: 10.1038/s41419-018-1291-5.
  29. Huang F, Zhang Q, Ma H, Lv Q, Zhang T. Expression of glutaminase is upregulated in colorectal cancer and of clinical significance. Int J Clin Exp Pathol. 2014;7(3):1093–100.
  30. Song Z, Wei B, Lu C, Li P, Chen L. Glutaminase sustains cell survival via the regulation of glycolysis and glutaminolysis in colorectal cancer. Oncol Lett. 2017;14(3):3117-23. doi: 10.3892/ol.2017.6538.
Middle East Journal of Cancer
Volume 15, Issue 1 - Serial Number 57
January 2024
Pages 15-24
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