Research Article
BibTex RIS Cite

Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer

Year 2021, Volume: 11 Issue: 3, 418 - 425, 27.09.2021
https://doi.org/10.33808/clinexphealthsci.756701

Abstract

Objective: EDIL3 expression levels are raised in some types of cancer which means that it can be used as a candidate tumor marker. Hypoxia upregulates tumor-associated carbonic anhydrases in cancer genesis. In this study, we aimed to investigate whether EDIL3 plays a role in the hypoxic microenvironment of pancreatic cancer.
Methods: Gene expression and mutation profiles of pancreatic cancer patients and healthy tissue samples were downloaded The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the EDIL3, HIF1A, CA IX and CA XII genes were analyzed. Additionally, PolyPhen-2 and SNAP tools were used to prediction and confirmation of detected alterations pathogenicity and survival analysis was performed.
Results: Expression level of EDIL3, HIF1A and CA IX were found to be statistically significant higher in the patient compared to healthy group and we showed also positive correlation between EDIL3 and HIF1A gene expression. Furthermore, low CA IX and CA XII expression level were found effective on overall survival (p<0.05). Additionally, 8 missense mutations were detected in the coding region of studied genes.
Conclusion: We suggested that relationship between EDIL3 and HIF1A in pancreatic cancer and EDIL3 is a novel molecule cancer development in pancreatic cancer.

Supporting Institution

Çalışma herhangi bir destek alınarak gerçekleştirilmemiştir.

Project Number

-

Thanks

-

References

  • 1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol 2019;10:10-27.
  • 2. Juiz NA, Iovanna J, Dusetti N. Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome. Front Oncol 2019;9:246.
  • 3. Makohon-Moore A, Iacobuzio-Donahue CA. Pancreatic cancer biology and genetics from an evolutionary perspective. Nat Rev Cancer 2016;16:553-65.
  • 4. Araos J, Sleeman JP, Garvalov BK. The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies. Clin Exp Metastasis 2018;35:563-599.
  • 5. Parks SK, Cormerais Y, Pouysségur J. Hypoxia and cellular metabolism in tumour pathophysiology. J Physiol 2017;595:2439-2450.
  • 6. Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity 2014;41:518-28.
  • 7. Petrova V, Annicchiarico-Petruzzelli M, Melino G, Amelio I. The hypoxic tumour microenvironment. Oncogenesis 2018;7:10.
  • 8. Al Tameemi W, Dale TP, Al-Jumaily RMK, Forsyth NR. Hypoxia-Modified Cancer Cell Metabolism. Front Cell Dev Biol 2019 29;7:4.
  • 9. Dengler VL, Galbraith M, Espinosa JM. Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol 2014;49:1-15.
  • 10. Mboge MY, Mahon BP, McKenna R, Frost SC. Carbonic Anhydrases: Role in pH Control and Cancer. Metabolites 2018; 28;8(1). pii: E19. 11. Waheed A, Sly WS. Carbonic anhydrase XII functions in health and disease. Gene 2017 5;623:33-40.
  • 12. Pastorekova S, Gillies RJ. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 2019;38(1-2):65-77.
  • 13. Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs 2018;27:963-970.
  • 14. Jiang SH, Wang Y, Yang JY, Li J, Feng MX, Wang YH, Yang XM, He P, Tian GA, Zhang XX, Li Q, Cao XY, Huo YM, Yang MW, Fu XL, Li J, Liu DJ, Dai M, Wen SY, Gu JR, Hong J, Hua R, Zhang ZG, Sun YW. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer. Oncotarget 2016;7(4):4226-40.
  • 15. Choi EY, Chavakis E, Czabanka MA, Langer HF, Fraemohs L, Economopoulou M, Kundu RK, Orlandi A, Zheng YY, Prieto DA, Ballantyne CM, Constant SL, Aird WC, Papayannopoulou T, Gahmberg CG, Udey MC, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T. Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science 2008;322(5904):1101-4.
  • 16. Kourtzelis I, Li X, Mitroulis I, Grosser D, Kajikawa T, Wang B, Grzybek M, von Renesse J, Czogalla A, Troullinaki M, Ferreira A, Doreth C, Ruppova K, Chen LS, Hosur K, Lim JH, Chung KJ, Grossklaus S, Tausche AK, Joosten LAB, Moutsopoulos NM, Wielockx B, Castrillo A, Korostoff JM, Coskun Ü, Hajishengallis G, Chavakis T. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol 2019;20(1):40-49.
  • 17. Jiang SH, Wang Y, Yang JY, Li J, Feng MX, Wang YH, Yang XM, He P, Tian GA, Zhang XX, Li Q, Cao XY, Huo YM, Yang MW, Fu XL, Li J, Liu DJ, Dai M, Wen SY, Gu JR, Hong J, Hua R, Zhang ZG, Sun YW. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer. Oncotarget 2016;7(4):4226-40.
  • 18. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2(5):401-4.
  • 19. Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, Dimitriadoy S, Liu DL, Kantheti HS, Saghafinia S, Chakravarty D, Daian F, Gao Q, Bailey MH, Liang WW, Foltz SM, Shmulevich I, Ding L, Heins Z, Ochoa A, Gross B, Gao J, Zhang H, Kundra R, Kandoth C, Bahceci I, Dervishi L, Dogrusoz U, Zhou W, Shen H, Laird PW, Way GP, Greene CS, Liang H, Xiao Y, Wang C, Iavarone A, Berger AH, Bivona TG, Lazar AJ, Hammer GD, Giordano T, Kwong LN, McArthur G, Huang C, Tward AD, Frederick MJ, McCormick F, Meyerson M; Cancer Genome Atlas Research Network, Van Allen EM, Cherniack AD, Ciriello G, Sander C, Schultz N. Oncogenic SignalingPathways in The Cancer Genome Atlas Cell 2018 ;173(2):321-337.e10.
  • 20. Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013; Chapter7:Unit7.20.
  • 21. Bromberg Y, Rost B. SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res 2007;35(11):3823-35.
  • 22. Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, Fish P, Harsha B, Hathaway C, Jupe SC, Kok CY, Noble K, Ponting L, Ramshaw CC, Rye CE, Speedy HE, Stefancsik R, Thompson SL, Wang S, Ward S, Campbell PJ, Forbes SA. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res 2019;47(D1):D941-D947.
  • 23. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102.
  • 24. Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.
  • 25. Tan Z, Xu J, Zhang B, Shi S, Yu X, Liang C. Hypoxia: a barricade to conquer the pancreatic cancer. Cell Mol Life Sci. 2020;6.
  • 26. Leppänen J, Helminen O, Huhta H, Kauppila JH, Isohookana J, Haapasaari KM, Parkkila S, Saarnio J, Lehenkari PP, Karttunen TJ. Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma. World J Surg Oncol 2018;16(1):127..
  • 27. Hoffmann AC, Mori R, Vallbohmer D, Brabender J, Klein E, Drebber U, Baldus SE, Cooc J, Azuma M, Metzger R, Hoelscher AH, Danenberg KD, Prenzel KL, Danenberg PV. High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia 2008;10(7):674-9.
Year 2021, Volume: 11 Issue: 3, 418 - 425, 27.09.2021
https://doi.org/10.33808/clinexphealthsci.756701

Abstract

Project Number

-

References

  • 1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol 2019;10:10-27.
  • 2. Juiz NA, Iovanna J, Dusetti N. Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome. Front Oncol 2019;9:246.
  • 3. Makohon-Moore A, Iacobuzio-Donahue CA. Pancreatic cancer biology and genetics from an evolutionary perspective. Nat Rev Cancer 2016;16:553-65.
  • 4. Araos J, Sleeman JP, Garvalov BK. The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies. Clin Exp Metastasis 2018;35:563-599.
  • 5. Parks SK, Cormerais Y, Pouysségur J. Hypoxia and cellular metabolism in tumour pathophysiology. J Physiol 2017;595:2439-2450.
  • 6. Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity 2014;41:518-28.
  • 7. Petrova V, Annicchiarico-Petruzzelli M, Melino G, Amelio I. The hypoxic tumour microenvironment. Oncogenesis 2018;7:10.
  • 8. Al Tameemi W, Dale TP, Al-Jumaily RMK, Forsyth NR. Hypoxia-Modified Cancer Cell Metabolism. Front Cell Dev Biol 2019 29;7:4.
  • 9. Dengler VL, Galbraith M, Espinosa JM. Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol 2014;49:1-15.
  • 10. Mboge MY, Mahon BP, McKenna R, Frost SC. Carbonic Anhydrases: Role in pH Control and Cancer. Metabolites 2018; 28;8(1). pii: E19. 11. Waheed A, Sly WS. Carbonic anhydrase XII functions in health and disease. Gene 2017 5;623:33-40.
  • 12. Pastorekova S, Gillies RJ. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 2019;38(1-2):65-77.
  • 13. Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs 2018;27:963-970.
  • 14. Jiang SH, Wang Y, Yang JY, Li J, Feng MX, Wang YH, Yang XM, He P, Tian GA, Zhang XX, Li Q, Cao XY, Huo YM, Yang MW, Fu XL, Li J, Liu DJ, Dai M, Wen SY, Gu JR, Hong J, Hua R, Zhang ZG, Sun YW. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer. Oncotarget 2016;7(4):4226-40.
  • 15. Choi EY, Chavakis E, Czabanka MA, Langer HF, Fraemohs L, Economopoulou M, Kundu RK, Orlandi A, Zheng YY, Prieto DA, Ballantyne CM, Constant SL, Aird WC, Papayannopoulou T, Gahmberg CG, Udey MC, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T. Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science 2008;322(5904):1101-4.
  • 16. Kourtzelis I, Li X, Mitroulis I, Grosser D, Kajikawa T, Wang B, Grzybek M, von Renesse J, Czogalla A, Troullinaki M, Ferreira A, Doreth C, Ruppova K, Chen LS, Hosur K, Lim JH, Chung KJ, Grossklaus S, Tausche AK, Joosten LAB, Moutsopoulos NM, Wielockx B, Castrillo A, Korostoff JM, Coskun Ü, Hajishengallis G, Chavakis T. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol 2019;20(1):40-49.
  • 17. Jiang SH, Wang Y, Yang JY, Li J, Feng MX, Wang YH, Yang XM, He P, Tian GA, Zhang XX, Li Q, Cao XY, Huo YM, Yang MW, Fu XL, Li J, Liu DJ, Dai M, Wen SY, Gu JR, Hong J, Hua R, Zhang ZG, Sun YW. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer. Oncotarget 2016;7(4):4226-40.
  • 18. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2(5):401-4.
  • 19. Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, Dimitriadoy S, Liu DL, Kantheti HS, Saghafinia S, Chakravarty D, Daian F, Gao Q, Bailey MH, Liang WW, Foltz SM, Shmulevich I, Ding L, Heins Z, Ochoa A, Gross B, Gao J, Zhang H, Kundra R, Kandoth C, Bahceci I, Dervishi L, Dogrusoz U, Zhou W, Shen H, Laird PW, Way GP, Greene CS, Liang H, Xiao Y, Wang C, Iavarone A, Berger AH, Bivona TG, Lazar AJ, Hammer GD, Giordano T, Kwong LN, McArthur G, Huang C, Tward AD, Frederick MJ, McCormick F, Meyerson M; Cancer Genome Atlas Research Network, Van Allen EM, Cherniack AD, Ciriello G, Sander C, Schultz N. Oncogenic SignalingPathways in The Cancer Genome Atlas Cell 2018 ;173(2):321-337.e10.
  • 20. Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013; Chapter7:Unit7.20.
  • 21. Bromberg Y, Rost B. SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res 2007;35(11):3823-35.
  • 22. Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, Fish P, Harsha B, Hathaway C, Jupe SC, Kok CY, Noble K, Ponting L, Ramshaw CC, Rye CE, Speedy HE, Stefancsik R, Thompson SL, Wang S, Ward S, Campbell PJ, Forbes SA. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res 2019;47(D1):D941-D947.
  • 23. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102.
  • 24. Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.
  • 25. Tan Z, Xu J, Zhang B, Shi S, Yu X, Liang C. Hypoxia: a barricade to conquer the pancreatic cancer. Cell Mol Life Sci. 2020;6.
  • 26. Leppänen J, Helminen O, Huhta H, Kauppila JH, Isohookana J, Haapasaari KM, Parkkila S, Saarnio J, Lehenkari PP, Karttunen TJ. Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma. World J Surg Oncol 2018;16(1):127..
  • 27. Hoffmann AC, Mori R, Vallbohmer D, Brabender J, Klein E, Drebber U, Baldus SE, Cooc J, Azuma M, Metzger R, Hoelscher AH, Danenberg KD, Prenzel KL, Danenberg PV. High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia 2008;10(7):674-9.
There are 26 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Dilara Fatma Akın 0000-0002-0903-0017

Rahsan Ilıkcı This is me 0000-0003-3844-6158

Project Number -
Publication Date September 27, 2021
Submission Date June 23, 2020
Published in Issue Year 2021 Volume: 11 Issue: 3

Cite

APA Akın, D. F., & Ilıkcı, R. (2021). Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer. Clinical and Experimental Health Sciences, 11(3), 418-425. https://doi.org/10.33808/clinexphealthsci.756701
AMA Akın DF, Ilıkcı R. Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer. Clinical and Experimental Health Sciences. September 2021;11(3):418-425. doi:10.33808/clinexphealthsci.756701
Chicago Akın, Dilara Fatma, and Rahsan Ilıkcı. “Mutations and Expression Profile of EDIL3 and Correlation With HIF1A and Tumor-Associated Carbonic Anhydrases in Pancreatic Cancer”. Clinical and Experimental Health Sciences 11, no. 3 (September 2021): 418-25. https://doi.org/10.33808/clinexphealthsci.756701.
EndNote Akın DF, Ilıkcı R (September 1, 2021) Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer. Clinical and Experimental Health Sciences 11 3 418–425.
IEEE D. F. Akın and R. Ilıkcı, “Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer”, Clinical and Experimental Health Sciences, vol. 11, no. 3, pp. 418–425, 2021, doi: 10.33808/clinexphealthsci.756701.
ISNAD Akın, Dilara Fatma - Ilıkcı, Rahsan. “Mutations and Expression Profile of EDIL3 and Correlation With HIF1A and Tumor-Associated Carbonic Anhydrases in Pancreatic Cancer”. Clinical and Experimental Health Sciences 11/3 (September 2021), 418-425. https://doi.org/10.33808/clinexphealthsci.756701.
JAMA Akın DF, Ilıkcı R. Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer. Clinical and Experimental Health Sciences. 2021;11:418–425.
MLA Akın, Dilara Fatma and Rahsan Ilıkcı. “Mutations and Expression Profile of EDIL3 and Correlation With HIF1A and Tumor-Associated Carbonic Anhydrases in Pancreatic Cancer”. Clinical and Experimental Health Sciences, vol. 11, no. 3, 2021, pp. 418-25, doi:10.33808/clinexphealthsci.756701.
Vancouver Akın DF, Ilıkcı R. Mutations and expression profile of EDIL3 and correlation with HIF1A and tumor-associated carbonic anhydrases in pancreatic cancer. Clinical and Experimental Health Sciences. 2021;11(3):418-25.

14639   14640