Yıl: 2022 Cilt: 5 Sayı: 3 Sayfa Aralığı: 137 - 151 Metin Dili: İngilizce DOI: 10.14744/ijmb.2022.18199 İndeks Tarihi: 14-10-2022

Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis

Öz:
Objectives: The scope of this study was to identify potential genes as a promising biomarker in diagnosing cholangiocarcinoma (CCA) or differentiating the subtypes of CCA. In this study, we used Gene Expression Omnibus (GEO)-NCBI data sets as promising open sources to perform integrative analysis. Methods: The gene expression data sets of intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) were retrieved from GEO, and the statistical analysis of GSE45001 (iCCA), GSE76311 (iCCA), and GSE132305 (eCCA) was performed to identify significantly expressed genes. The association of listed genes with CCA was checked via text-mining approaches. For CCA, the details were provided by discussing its relations with our results. Then, the pathway analysis was performed to identify common pathways both in iCCA and eCCA. Results: The pathway analysis reveals that although there are common pathways between iCCA and eCCA, the associated genes within these pathways are different from one another. According to the results of upregulated gene sets, integrin cell surface interaction (R-HSA-216083), MET activates PTK2 signaling (R-HSA-8874081), degradation of the extracellular matrix (ECM) (R-HSA-1474228), nonintegrin membrane–ECM interaction (R-HSA-3000171), and assembly of collagen fibrils and other multimeric structures (R-HSA-2022090) are found as common pathways among these data sets, yet there is no reported common pathway within downregulated gene sets. A detailed study of common pathway analysis shows that COL1A1 and COL1A2 genes, whose associations with CCA have not been reported, seem promising to differentiate iCCA from eCCA. The pathway analysis also reveals that although there are common pathways between iCCA and eCCA, the associated genes within these pathways are different from one another. Conclusion: Focusing on pathways rather than genes is more promising for revealing the potential biomarkers together with providing a deeper understanding by highlighting significant pathways.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov 2017;7(10):1116–35.
  • 2. Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet 2005;366(9493):1303–14.
  • 3. Mosconi S, Beretta GD, Labianca R, Zampino MG, Gatta G, Heinemann V. Cholangiocarcinoma. Crit Rev Oncol Hematol 2009;69(3):259–70.
  • 4. Macias RIR, Kornek M, Rodrigues PM, Paiva NA, Castro RE, Urban S., et al. Diagnostic and prognostic biomarkers in cholangiocarcinoma. Liver Int 2019;39(Suppl 1):108–22.
  • 5. Waddell SH, Boulter L. Developing models of cholangiocarcinoma to close the translational gap in cancer research. Expert Opin Investig Drugs 2021;30(4):439–50.
  • 6. Bratulic S, Gatto F, Nielsen J. The translational status of cancer liquid biopsies. Regen Eng Transl Med 2021;7(3):312–52.
  • 7. Schiffman JD, Fisher PG, Gibbs P. Early detection of cancer: past, present, and future. Am Soc Clin Oncol Educ Book 2015;57–65.
  • 8. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS 2010;5(6):463.
  • 9. Vedeld HM, Grimsrud MM, Andresen K, Phara HD, Seth EV, Karlsen TH, et al. Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile. Hepatology 2022;75(1):59–73.
  • 10. Nation JB, Cabot-Miller J, Segal O, Lucito R, Adaricheva K. Combining algorithms to find signatures that predict risk in early-stage stomach cancer. J Comput Biol 2021;28(10):985– 1006.
  • 11. Vedeld HM, Andresen K, Eilertsen IA, Eilertsen IA, Nesbakken A, Seruca R, et al. The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers. Int J Cancer 2015;136(4):844–53.
  • 12. Tshering G, Dorji PW, Chaijaroenkul W, Na-Bangchang K. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review. Am J Trop Med Hyg 2018;98(6):1788–97.
  • 13. Barrett T, Suzek TO, Troup DB, Wilhite SE, Ngau WC, Ledoux P, et al. NCBI GEO: mining millions of expression profiles--database and tools. Nucleic Acids Res 2005;33(Database issue):D562–6.
  • 14. Joshi-Tope G, Gillespie M, Vastrik I, D'Eustachio P, Schmidt E, de Bono B, et al. Reactome: a knowledgebase of biological pathways. Nucleic Acids Res 2005;33(Database issue):D428–32.
  • 15. Augen J. Bioinformatics in the post-genomic era: Genome, transcriptome, proteome, and information-based medicine. Boston: Addison Wesley Professional; 2004. p. 388.
  • 16. Pei YF, Liu J, Cheng J, Wu WD, Liu XQ. Silencing of LAMC2 reverses epithelial-mesenchymal transition and inhibits angiogenesis in cholangiocarcinoma via inactivation of the epidermal growth factor receptor signaling pathway. Am J Pathol 2019;189(8):1637–53.
  • 17. Fujimoto K, Kawaguchi T, Nakashima O, Ono J, Ohta S, Kawaguchi A, et al. Periostin, a matrix protein, has potential as a novel serodiagnostic marker for cholangiocarcinoma. Oncol Rep 2011;25(5):1211–6.
  • 18. Utispan K, Sonongbua J, Thuwajit P, Chau-In S, Pairojkul C, Wongkham S, et al. Periostin activates integrin α5β1 through a PI3K/AKT-dependent, pathway in invasion of cholangiocarcinoma. Int J Oncol 2012;41(3):1110–8.
  • 19. Utispan K, Thuwajit P, Abiko Y, Charngkaew K, Pairojkul A, Chau-In S, et al. Gene expression profiling of cholangiocarcinoma- derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol Cancer 2010;24;9:13.
  • 20. Uenishi T, Yamazaki O, Tanaka H, Takemura S, Yamamoto T, Tanaka S, et al. Serum cytokeratin 19 fragment (CYFRA21-1) as a prognostic factor in intrahepatic cholangiocarcinoma. Ann Surg Oncol 2008;15(2):583–9.
  • 21. Huang L, Chen W, Liang P, Hu W, Zhang K, Shen S, et al. Serum CYFRA 21-1 in biliary tract cancers: a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma. Dig Dis Sci 2015;60(5):1273–83.
  • 22. Abe T, Amano H, Shimamoto F, Hattori M, Kuroda S, Kobayashi T, et al. Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy. Eur J Surg Oncol 2015;41(11):1515–21.
  • 23. Xu HL, Inagaki Y, Seyama Y, Sugawara Y, Kokudo N, Nakata M, et al. Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion. Life Sci 2009;85(9- 10):395–400.
  • 24. Suwanmanee G, Yosudjai J, Phimsen S, Wongkham S, Jirawatnotai S, Kaewkong W. Upregulation of AGR2vH facilitates cholangiocarcinoma cell survival under endoplasmic reticulum stress via the activation of the unfolded protein response pathway. Int J Mol Med 2020;45(2):669–77.
  • 25. Yosudjai J, Inpad C, Chomwong S, Dana P, Sawanyawisuth K, Phimsen S, et al. An aberrantly spliced isoform of anterior gradient- 2, AGR2vH promotes migration and invasion of cholangiocarcinoma cell. Biomed Pharmacother 2018;107:109–16.
  • 26. Itatsu K, Zen Y, Yamaguchi J, Ohira S, Ishikawa A, Ikeda H, et al. Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts. Hum Pathol 2008;39(5):710–9.
  • 27. Sun Q, Gong X, Wu J, Hu Z, Zhang Q, Gong J, et al. Effect of lncRNA PVT1/miR186/KLF5 axis on the occurrence and progression of cholangiocarcinoma. Biomed Res Int 2021:8893652
  • 28. Terashi T, Aishima S, Taguchi K, Asayama Y, Sugimachi K, Matsuura S, et al. Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma. Liver Int 2004;24(1):38–45.
  • 29. Thanee M, Dokduang H, Kittirat Y, Pjetcharaburanin J, Klanrit P, Titapun A, et al. CD44 modulates metabolic pathways and altered ROS-mediated Akt signal promoting cholangiocarcinoma progression. PLos One 2021;16(3):e0245871
  • 30. Franken LC, Vuijk FA, Soer EC, Roos E, Erdman JI, Hoojer GKJ, et al. Expression of integrin ανβ6 differentiates perihilar cholangiocarcinoma (PHC) from benign disease mimicking PHC. Eur J Surg Oncol 2021;47(3):628–34.
  • 31. Pak JH, Bashir Q, Kim IK, Hong Sj, Maeng S, Bahk YY, et al. Clonorchis sinensis excretory-secretory products promote the migration and invasion of cholangiocarcinoma cells by activating the integrin β4–FAK/Src signaling pathway. Mol Biochem Parasitol 2017;214:1–9.
  • 32. Tanaka M, Shibahara J, Ishikawa S, Ushiku T, Morikawa T, Shinozaki-Ushiku A, et al. EVI1 expression is associated with aggressive behavior in intrahepatic cholangiocarcinoma. Virchows Arch 2018;474(1):39–46.
  • 33. Takamura. Loss of liver-intestine cadherin in human intrahepatic cholangiocarcinoma promotes angiogenesis by up-regulating metal-responsive transcription factor-1 and placental growth factor. Int J Oncol 2010;36(1):245–54.
  • 34. Shi X de, Yu X huan, Wu W rui, Xu XL, Wang JY, Xu LB, et al. Dickkopf-1 expression is associated with tumorigenity and lymphatic metastasis in human hilar cholangiocarcinoma. Oncotarget 2016;7(43):70378–87.
  • 35. Yonglitthipagon P, Pairojkul C, Chamgramol Y, Mulvenna J, Sripa B. Up-regulation of annexin A2 in cholangiocarcinoma caused by Opisthorchis viverrini and its implication as a prognostic marker. Int J Parasitol 2010;40(10):1203–12.
  • 36. Peng C, Sun Z, Li O, Guo C, Yi W, Tan Z, et al. Leptin stimulates the epithelial mesenchymal transition and pro angiogenic capability of cholangiocarcinoma cells through the miR 122/ PKM2 axis. Int J Oncol 2019;55(1):298–308.
  • 37. Sasaki M, Tsuneyama K, Nakanuma Y. Aberrant expression of trefoil factor family 1 in biliary epithelium in hepatolithiasis and cholangiocarcinoma. Lab Investig 2003;83(10):1403–13.
  • 38. Dai R, Li J, Fu J, Chen Y, Wang R, Zhao X, et al. The tyrosine kinase c-Met contributes to the pro-tumorigenic function of the p38 kinase in human bile duct cholangiocarcinoma cells. J Biol Chem 2012;287(47):39812–23.
  • 39. Deng G, Zhu L, Huang F, Nie W, Huang W, Xu H, et al. SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma. Oncotarget 2015;6(29):27416–26.
  • 40. Tanaka Y, Aishima S, Kohashi K, Okumura Y, Wang H, Hida T, et al. Spalt-like transcription factor 4 immunopositivity is associated with epithelial cell adhesion molecule expression in combined hepatocellular carcinoma and cholangiocarcinoma. Histopathology 2016;68(5):693–701.
  • 41. Wang W, Liu Y, Liao K. Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility. BMC Cell Biol 2011;12:49.
  • 42. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 2006;69(3):562– 73.
  • 43. Birk DE, Brückner P. Collagens, suprastructures, and collagen fibril assembly. Extracell Matrix an Overv 2011:77–115.
  • 44. Kadler KE, Holmes DF, Trotter JA, Chapman JA. Collagen fibril formation. Biochem J 1996;316(Pt 1):1–11.
  • 45. Revell CK, Jensen OE, Shearer T, Lu Y, Holmes DF, Kadler KE. Collagen fibril assembly: New approaches to unanswered questions. Matrix Biol Plus 2021;12:100079.
  • 46. Shoulders MD, Raines RT. Collagen structure and stability . Annu Rev Biochem 2009;78:929–58.
  • 47. Culbert AA, Lowe MP, Atkinson M, Byers PH, Wallis GA, Kadler KE. Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro α1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite. Biochem J 1995;311(3):815–20.
  • 48. Banerjee S, Karunagaran D. An integrated approach for mining precise RNA-based cervical cancer staging biomarkers. Gene. 2019;712:143961.
APA YENENLER-KUTLU A, Arda M, Atak E, Ulukaya E (2022). Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. , 137 - 151. 10.14744/ijmb.2022.18199
Chicago YENENLER-KUTLU ASLI,Arda Merve,Atak Evren,Ulukaya Engin Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. (2022): 137 - 151. 10.14744/ijmb.2022.18199
MLA YENENLER-KUTLU ASLI,Arda Merve,Atak Evren,Ulukaya Engin Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. , 2022, ss.137 - 151. 10.14744/ijmb.2022.18199
AMA YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. . 2022; 137 - 151. 10.14744/ijmb.2022.18199
Vancouver YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. . 2022; 137 - 151. 10.14744/ijmb.2022.18199
IEEE YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E "Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis." , ss.137 - 151, 2022. 10.14744/ijmb.2022.18199
ISNAD YENENLER-KUTLU, ASLI vd. "Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis". (2022), 137-151. https://doi.org/10.14744/ijmb.2022.18199
APA YENENLER-KUTLU A, Arda M, Atak E, Ulukaya E (2022). Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. International Journal of Medical Biochemistry, 5(3), 137 - 151. 10.14744/ijmb.2022.18199
Chicago YENENLER-KUTLU ASLI,Arda Merve,Atak Evren,Ulukaya Engin Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. International Journal of Medical Biochemistry 5, no.3 (2022): 137 - 151. 10.14744/ijmb.2022.18199
MLA YENENLER-KUTLU ASLI,Arda Merve,Atak Evren,Ulukaya Engin Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. International Journal of Medical Biochemistry, vol.5, no.3, 2022, ss.137 - 151. 10.14744/ijmb.2022.18199
AMA YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. International Journal of Medical Biochemistry. 2022; 5(3): 137 - 151. 10.14744/ijmb.2022.18199
Vancouver YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis. International Journal of Medical Biochemistry. 2022; 5(3): 137 - 151. 10.14744/ijmb.2022.18199
IEEE YENENLER-KUTLU A,Arda M,Atak E,Ulukaya E "Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis." International Journal of Medical Biochemistry, 5, ss.137 - 151, 2022. 10.14744/ijmb.2022.18199
ISNAD YENENLER-KUTLU, ASLI vd. "Identification of key genes and pathways for cholangiocarcinoma using an integrated bioinformatics analysis". International Journal of Medical Biochemistry 5/3 (2022), 137-151. https://doi.org/10.14744/ijmb.2022.18199