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KOLOREKTAL KANSERDE sFRP-4, TFF-3, NF-κB ve ROMO1 DÜZEYLERİNİN ROLÜNÜN ARAŞTIRILMASI: HASTALIĞIN PATOFİZYOLOJİSİ VE PROGRESYONUNA ETKİLERİ

Year 2024, , 120 - 126, 29.02.2024
https://doi.org/10.53446/actamednicomedia.1391225

Abstract

Amaç: Kolorektal kanser (KRK), yüksek morbidite ve mortalite oranları ile önemli bir küresel sağlık sorunudur. Erken teşhis ve doğru tanı araçları klinik seyrin yönetimi için kritik öneme sahiptir. Bu araştırma, geleneksel tanı yaklaşımlarının ötesinde bilgiler sağlamayı amaçlayarak KRK'nin moleküler manzarasını araştırmaktadır. Bu çalışmanın temel amacı, salgılanan frizzled ilişkili protein-4 (sFRP-4), trefoil faktör-3 (TFF-3), nükleer faktör-kappa-B (NF-κB) ve reaktif oksijen türleri modülatörü-1 (Romo1) gibi spesifik biyobelirteçlerin, KRK’nin patofizyolojisini anlamaya ve progresyonunu belirlemeye potansiyel katkılarını araştırmaktır.
Yöntem: Bu çalışmada, KRK'li hastalar (n=50) ile yaş ve cinsiyet açısından eşleştirilmiş kontrol grubunda (n=40) sFRP-4, TFF-3, NF-κB ve Romo1'in plazma düzeyleri ELISA yöntemi ile analiz edilmiştir. Bu biyobelirteçlerin tanısal performansı ROC analizi ile değerlendirilmiştir.
Bulgular: Araştırmamız, KRK tanısı alan hastalarda NF-κB, TFF-3 ve Romo1 seviyelerinde önemli bir artış olduğunu ortaya koymuştur. Ayrıca, bu parametrelerin 4 cm'den büyük tümörü olan hastalarda daha küçük tümörü olanlara kıyasla daha yüksek seviyelerde olduğu tespit edilmiştir. Metastazı olan hastalarda da metastazı olmayan hastalara kıyasla üç parametrenin seviyeleri de yüksek bulunmuştur. ROC analizi, NF-κB'nin hastaları kontrol bireylerinden ayırt etmek için potansiyeli en iyi biyobelirteç olabileceğini, TFF-3'ün ise tümör boyutunu ve metastaz varlığını belirlemede en fazla potansiyel gösterdiğini ortaya koymuştur.
Sonuç: Bu araştırma, KRK'nın patofizyolojisinin ve progresyonunun anlaşılmasına katkı sağlamaktadır. Çalışmamızda ortaya konduğu üzere NF-κB, TFF-3 ve Romo1'in biyobelirteç olarak potansiyel rolleri, KRK'nin erken teşhisi ve yönetimi için umut verici bir yaklaşım sunmaktadır. Bu biyobelirteçlerin KRK'nin patofizyolojik mekanizmasındaki rollerini netleştirmek ve klinik faydalarını belirlemek için daha fazla doğrulama ve ileriye dönük çalışmalar gereklidir.

References

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  • 14. Li Q, Wang K, Su C, Fang J. Serum Trefoil Factor 3 as a Protein Biomarker for the Diagnosis of Colorectal Cancer. Technol Cancer Res Treat. 2017;16(4):440-445. doi:10.1177/1533034616674323
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  • 21. Soly W, Zhanjie L, Lunshan W, Xiaoren Z. NF-κB Signaling Pathway, Inflammation and Colorectal Cancer. Cell Mol Immunol 2009 65. 2009;6(5):327-334. doi:10.1038/cmi.2009.43
  • 22. Xia L, Tan S, Zhou Y, et al. Role of the NFκB-signaling pathway in cancer. Onco Targets Ther. 2018;11:2063. doi:10.2147/OTT.S161109
  • 23. Harrington BS, Annunziata CM. NF-κB Signaling in Ovarian Cancer. Cancers (Basel). 2019;11(8). doi:10.3390/CANCERS11081182
  • 24. Puvvada SD, Funkhouser WK, Greene K, et al. NF-ĸB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer. Oncology. 2010;78(3-4):181-188. doi:10.1159/000313697
  • 25. Klampfer L. Cytokines, Inflammation and Colon Cancer. Curr Cancer Drug Targets. 2011;11(4):451-464. doi:10.2174/156800911795538066
  • 26. Ghasemi H, Amini MA, Pegah A, et al. Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer. Mol Biol Rep. 2020;47(9):6497. doi:10.1007/S11033-020-05702-1
  • 27. Tsoneva E, Dimitrova PD, Metodiev M, Shivarov V, Vasileva-Slaveva M, Yordanov A. The effects of ROMO1 on cervical cancer progression. Pathol - Res Pract. 2023;248:154561. doi:10.1016/J.PRP.2023.154561
  • 28. Betteridge DJ. What is oxidative stress? Metabolism. 2000;49(2):3-8. doi:10.1016/S0026-0495(00)80077-3
  • 29. Jo MJ, Kim BG, Park SH, et al. Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer. Cancers 2020, Vol 12, Page 2358. 2020;12(9):2358. doi:10.3390/CANCERS12092358
  • 30. Chung JS, Park S, Park SH, et al. Overexpression of Romo1 Promotes Production of Reactive Oxygen Species and Invasiveness of Hepatic Tumor Cells. Gastroenterology. 2012;143(4):1084-1094.e7. doi:10.1053/J.GASTRO.2012.06.038
  • 31. Jo MJ, Kim BG, Park SH, et al. Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer. Cancers (Basel). 2020;12(9):1-18. doi:10.3390/CANCERS12092358
  • 32. Chen YH, Lu Y, De Plaen IG, Wang LY, Tan X Di. Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells. Biochem Biophys Res Commun. 2000;274(3):576-582. doi:10.1006/BBRC.2000.3176
  • 33. Rong Z, Zaihong Y, Gastroenterology ZJD of, Corporation the CH of CNP, 065000 L, China. Expressions of TFF3,NF-κB and their implications in Helicobacter pylori associated-gastric ulcer and gastric cancer. Chinese J Gastroenterol Hepatol. 2013;(2):130-132.
  • 34. Yusufu A, Shayimu P, Tuerdi R, Fang C, Wang F, Wang H. TFF3 and TFF1 expression levels are elevated in colorectal cancer and promote the malignant behavior of colon cancer by activating the EMT process. Int J Oncol. 2019;55(4):789. doi:10.3892/IJO.2019.4854
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  • 37. Kondo S, Araki T, Toiyama Y, et al. Downregulation of trefoil factor-3 expression in the rectum is associated with the development of ulcerative colitis-associated cancer. Oncol Lett. 2018;16(3):3658. doi:10.3892/OL.2018.9120
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  • 39. Busuttil RA, George J, House CM, et al. SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence. Gastric Cancer. 2021;24(3):589. doi:10.1007/S10120-020-01143-8
  • 40. Bernreuther C, Daghigh F, Möller K, et al. Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions. Pathol Oncol Res. 2020;26(4):2709. doi:10.1007/S12253-020-00861-9
  • 41. Turan H, Vitale SG, Kahramanoglu I, et al. Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study. Arch Gynecol Obstet. 2022;306(6):2105. doi:10.1007/S00404-022-06563-8

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

Year 2024, , 120 - 126, 29.02.2024
https://doi.org/10.53446/actamednicomedia.1391225

Abstract

Objective: Colorectal cancer (CRC) is a significant global health concern with high morbidity and mortality rates. Early detection and accurate diagnostic tools are critical for managing the clinical course. This research explores the molecular landscape of CRC, aiming to provide valuable insights beyond traditional diagnostic approaches. The main aim of this study was to investigate the potential contribution of specific biomarkers, such as secreted frizzled associated protein-4 (sFRP-4), trefoil factor-3 (TFF-3), nuclear factor-kappa-B (NF-κB) and reactive oxygen species modulator-1 (Romo1), to understanding the pathophysiology and determining the progression of CRC.
Methods: This study analyzed plasma levels of sFRP-4, TFF-3, NF-κB and Romo1 in a cohort of patients with CRC (n=50) and age- and gender-matched control group (n=40), utilizing ELISA. The diagnostic performance of these biomarkers was assessed through Receiver Operating Characteristic (ROC) analysis.
Results: Our research revealed a significant increase in the levels of NF-κB, TFF-3 and Romo1 in patients with a diagnosis of CRC. Furthermore, these parameters were found to maintain elevated levels in patients with tumors larger than 4 cm as opposed to those with smaller tumors. Patients with metastases also had elevated levels of the three parameters compared with patients without metastases. The ROC analysis revealed that NF-κB showed the most promise as a parameter for distinguishing patients from control subjects, whereas TFF-3 displayed the most potential in identifying tumor size and the presence of metastasis.
Conclusion: This research contributes valuable insights into understanding the pathophysiology and progression of CRC. The potential roles of NF-κB, TFF-3, and Romo1 as biomarkers, as revealed in our study, offer a promising avenue for early detection and improved management of CRC. Further validation and prospective studies are necessary to clarify the roles of these biomarkers in the pathophysiological mechanism of CRC and to establish their clinical utility.

References

  • 1. Simon K. Colorectal cancer development and advances in screening. Clin Interv Aging. 2016;11:967. doi:10.2147/CIA.S109285
  • 2. Hossain MS, Karuniawati H, Jairoun AA, et al. Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers (Basel). 2022;14(7):1732. doi:10.3390/CANCERS14071732
  • 3. Zhang Y, Wang Y, Zhang B, Li P, Zhao Y. Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer. Biomed Pharmacother. 2023;163:114786. doi:10.1016/J.BIOPHA.2023.114786
  • 4. Gude SS, Veeravalli RS, Vejandla B, Gude SS, Venigalla T, Chintagumpala V. Colorectal Cancer Diagnostic Methods: The Present and Future. Cureus. 2023;15(4). doi:10.7759/CUREUS.37622
  • 5. Mo S, Dai W, Wang H, et al. Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study. eClinicalMedicine. 2023;55. doi:10.1016/j.eclinm.2022.101717
  • 6. Pawar NM, Rao P. Secreted frizzled related protein 4 (sFRP4) update: A brief review. Cell Signal. 2018;45:63-70. doi:10.1016/J.CELLSIG.2018.01.019
  • 7. Jones SE, Jomary C. Secreted Frizzled-related proteins: searching for relationships and patterns. BioEssays. 2002;24(9):811-820. doi:10.1002/BIES.10136
  • 8. Qi J, Zhu YQ, Luo J, Tao WH. Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor. World J Gastroenterol. 2006;12(44):7113-7117. doi:10.3748/WJG.V12.I44.7113
  • 9. Liu Y, Yu J, Xie Y, et al. EZH2 regulates sFRP4 expression without affecting the methylation of sFRP4 promoter DNA in colorectal cancer cell lines. Exp Ther Med. 2020;20(5):1-1. doi:10.3892/ETM.2020.9160
  • 10. Huang D, Yu B, Deng Y, et al. SFRP4 was overexpressed in colorectal carcinoma. J Cancer Res Clin Oncol. 2010;136(3):395-401. doi:10.1007/S00432-009-0669-2
  • 11. Nfonsam LE, Jandova J, Jecius HC, Omesiete PN, Nfonsam VN. SFRP4 expression correlates with epithelial mesenchymal transition-linked genes and poor overall survival in colon cancer patients. World J Gastrointest Oncol. 2019;11(8):589. doi:10.4251/WJGO.V11.I8.589
  • 12. Taupin D, Podolsky DK. Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol. 2003;4(9):721-732. doi:10.1038/NRM1203
  • 13. Yusup A, Huji B, Fang C, et al. Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol. 2017;23(1):110-120. doi:10.3748/WJG.V23.I1.110
  • 14. Li Q, Wang K, Su C, Fang J. Serum Trefoil Factor 3 as a Protein Biomarker for the Diagnosis of Colorectal Cancer. Technol Cancer Res Treat. 2017;16(4):440-445. doi:10.1177/1533034616674323
  • 15. Hassanzadeh P. Colorectal cancer and NF-κB signaling pathway. Gastroenterol Hepatol From Bed to Bench. 2011;4(3):127. Accessed November 14, 2023. /pmc/articles/PMC4017424/
  • 16. Slattery ML, Mullany LE, Sakoda L, et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol. 2018;144(2):269. doi:10.1007/S00432-017-2548-6
  • 17. Huber MA, Azoitei N, Baumann B, et al. NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569. doi:10.1172/JCI21358
  • 18. Kim HJ, Jo MJ, Kim BR, et al. Reactive oxygen species modulator-1 (Romo1) predicts unfavorable prognosis in colorectal cancer patients. PLoS One. 2017;12(5). doi:10.1371/JOURNAL.PONE.0176834
  • 19. Shyamsunder P, Verma RS, Lyakhovich A. ROMO1 regulates RedOx states and serves as an inducer of NF-κB-driven EMT factors in Fanconi anemia. Cancer Lett. 2015;361(1):33-38. doi:10.1016/J.CANLET.2015.02.020
  • 20. Amin MB, Frederick ;, Greene L, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/CAAC.21388
  • 21. Soly W, Zhanjie L, Lunshan W, Xiaoren Z. NF-κB Signaling Pathway, Inflammation and Colorectal Cancer. Cell Mol Immunol 2009 65. 2009;6(5):327-334. doi:10.1038/cmi.2009.43
  • 22. Xia L, Tan S, Zhou Y, et al. Role of the NFκB-signaling pathway in cancer. Onco Targets Ther. 2018;11:2063. doi:10.2147/OTT.S161109
  • 23. Harrington BS, Annunziata CM. NF-κB Signaling in Ovarian Cancer. Cancers (Basel). 2019;11(8). doi:10.3390/CANCERS11081182
  • 24. Puvvada SD, Funkhouser WK, Greene K, et al. NF-ĸB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer. Oncology. 2010;78(3-4):181-188. doi:10.1159/000313697
  • 25. Klampfer L. Cytokines, Inflammation and Colon Cancer. Curr Cancer Drug Targets. 2011;11(4):451-464. doi:10.2174/156800911795538066
  • 26. Ghasemi H, Amini MA, Pegah A, et al. Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer. Mol Biol Rep. 2020;47(9):6497. doi:10.1007/S11033-020-05702-1
  • 27. Tsoneva E, Dimitrova PD, Metodiev M, Shivarov V, Vasileva-Slaveva M, Yordanov A. The effects of ROMO1 on cervical cancer progression. Pathol - Res Pract. 2023;248:154561. doi:10.1016/J.PRP.2023.154561
  • 28. Betteridge DJ. What is oxidative stress? Metabolism. 2000;49(2):3-8. doi:10.1016/S0026-0495(00)80077-3
  • 29. Jo MJ, Kim BG, Park SH, et al. Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer. Cancers 2020, Vol 12, Page 2358. 2020;12(9):2358. doi:10.3390/CANCERS12092358
  • 30. Chung JS, Park S, Park SH, et al. Overexpression of Romo1 Promotes Production of Reactive Oxygen Species and Invasiveness of Hepatic Tumor Cells. Gastroenterology. 2012;143(4):1084-1094.e7. doi:10.1053/J.GASTRO.2012.06.038
  • 31. Jo MJ, Kim BG, Park SH, et al. Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer. Cancers (Basel). 2020;12(9):1-18. doi:10.3390/CANCERS12092358
  • 32. Chen YH, Lu Y, De Plaen IG, Wang LY, Tan X Di. Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells. Biochem Biophys Res Commun. 2000;274(3):576-582. doi:10.1006/BBRC.2000.3176
  • 33. Rong Z, Zaihong Y, Gastroenterology ZJD of, Corporation the CH of CNP, 065000 L, China. Expressions of TFF3,NF-κB and their implications in Helicobacter pylori associated-gastric ulcer and gastric cancer. Chinese J Gastroenterol Hepatol. 2013;(2):130-132.
  • 34. Yusufu A, Shayimu P, Tuerdi R, Fang C, Wang F, Wang H. TFF3 and TFF1 expression levels are elevated in colorectal cancer and promote the malignant behavior of colon cancer by activating the EMT process. Int J Oncol. 2019;55(4):789. doi:10.3892/IJO.2019.4854
  • 35. Cui HY, Wang SJ, Song F, et al. CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression. Signal Transduct Target Ther 2021 61. 2021;6(1):1-15. doi:10.1038/s41392-021-00677-2
  • 36. Yang T, Fu X, Tian RF, et al. TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3. Transl Cancer Res. 2023;12(6):1503-1515. doi:10.21037/TCR-22-2552/COIF
  • 37. Kondo S, Araki T, Toiyama Y, et al. Downregulation of trefoil factor-3 expression in the rectum is associated with the development of ulcerative colitis-associated cancer. Oncol Lett. 2018;16(3):3658. doi:10.3892/OL.2018.9120
  • 38. Kida H, Jiang JJ, Matsui Y, et al. Dupuytren’s contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development. Int Immunol. 2023;35(7):303-312. doi:10.1093/INTIMM/DXAD004
  • 39. Busuttil RA, George J, House CM, et al. SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence. Gastric Cancer. 2021;24(3):589. doi:10.1007/S10120-020-01143-8
  • 40. Bernreuther C, Daghigh F, Möller K, et al. Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions. Pathol Oncol Res. 2020;26(4):2709. doi:10.1007/S12253-020-00861-9
  • 41. Turan H, Vitale SG, Kahramanoglu I, et al. Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study. Arch Gynecol Obstet. 2022;306(6):2105. doi:10.1007/S00404-022-06563-8
There are 41 citations in total.

Details

Primary Language English
Subjects Proteomics and Intermolecular Interactions
Journal Section Research Articles
Authors

Sinem Durmuş 0000-0002-9272-9098

Berrin Papila Kundaktepe 0000-0003-4394-3976

Remise Gelişgen 0000-0003-4121-5107

Çiğdem Papila 0000-0003-3837-7113

Hafize Uzun 0000-0002-1347-8498

Publication Date February 29, 2024
Submission Date November 16, 2023
Acceptance Date February 7, 2024
Published in Issue Year 2024

Cite

AMA Durmuş S, Papila Kundaktepe B, Gelişgen R, Papila Ç, Uzun H. EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION. Acta Med Nicomedia. February 2024;7(1):120-126. doi:10.53446/actamednicomedia.1391225

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