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Variabilita počtu kopií genů a léčebná odpověď na chemoterapii a bevacizumab u českých pacientů s metastatickým karcinomem kolorekta


Autoři: J. Stránská 1,2;  K. Bartáková 1;  Z. Rožánková 1;  L. Kotková 1;  J. Vrbková 1;  R. Trojanec 1;  P. Flodr 3;  H. Jurtíková 1,2;  B. Líznerová 1,2;  J. Drábek 1,2
Působiště autorů: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic 1;  University Hospital Olomouc, Czech Republic 2;  Institute of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic 3
Vyšlo v časopise: Klin Onkol 2024; 37(4): 277-285
Kategorie: Původní práce
doi: https://doi.org/10.48095/ccko2024277

Souhrn

Východiska: Přestože je bevacizumab prvním biologickým léčivem schváleným pro léčbu metastatického kolorektálního karcinomu (mCRC), neexistuje žádný zavedený DNA biomarker, který by zlepšil jeho účinnost a personalizoval léčbu. Materiál a metody: Sledováno bylo 30 pacientů s mCRC na terapii bevacizumabem (15 s dobrou odpovědí a 15 se špatnou odpovědí) z Fakultní nemocnice Olomouc. Pro analýzu variací v počtu kopií genů (copy number variation –⁠ CNV) byly použity vzorky FFPE a OncoScan FFPE Assay Kit, který zachycuje přibližně 900 nádorových genů. Výsledky: Ve skupině dobře reagujících pacientů bylo jako potenciálně významné pozitivní prediktivní nádorové biomarkery léčby bevacizumabem identifikováno 102 genů (klasifikovaných jako ATPázy, typ AAA, neuronální přenos signálu, regulace transkripce a domény typu PH superior). Ve špatně reagující skupině bylo identifikováno 74 potenciálně negativních prediktivních genů (klasifikovaných jako galektiny, signální dráha Jak-STAT, kaskáda MAPK, diferenciace a doména asociovaná s F-boxem). Závěr: V pilotní studii jsme našli slibné biomarkery variace počtu kopií odpovědi na bevacizumab v FFPE vzorcích nádorů pacientů s mCRC. Validační fáze by měla být zaměřena zejména na geny spojené s angiogenezí (AGRN, MAPK8, ARHGAP22, LGALS13, LGALS4, ZFP36 a MYC), tumorigenezí (DVL1) a proliferací tumoru (IFNL1, IFNL2, IFNL3, MAP3K10 a MAP4K1).

Klíčová slova:

bevacizumab – kolorektální karcinom – variabilita počtu kopií segmentů DNA


Zdroje

1. Willett CG, Boucher Y, di Tomaso E et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004; 10 (2): 145–147. doi: 10.1038/nm988.

2. Selvakumaran M, Yao KS, Feldman MD et al. Antitumor effect of the angiogenesis inhibitor bevacizumab is dependent on susceptibility of tumors to hypoxia-induced apoptosis. Biochem Pharmacol 2008; 75 (3): 627–638. doi: 10.1016/j.bcp.2007.09.029.

3. Luo HY, Xu RH. Predictive and prognostic biomarkers with therapeutic targets in advanced colorectal cancer. World J Gastroenterol 2014; 20 (14): 3858–3874. doi: 10.3748/wjg.v20.i14.3858.

4. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA 2021; 325 (7): 669–685. doi: 10.1001/jama.2021.0106.

5. Arnold D, Lueza B, Douillard JY et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol 2017; 28 (8): 1713–1729. doi: 10.1093/annonc/mdx175.

6. Cervantes A, Adam R, Roselló S et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34 (1): 10–32. doi: 10.1016/j.annonc.2022.10.003.

7. Garcia J, Hurwitz HI, Sandler AB et al. Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook. Cancer Treat Rev 2020; 86 : 102017. doi: 10.1016/j.ctrv.2020.102017.

8. Baltruškevičienė E, Mickys U, Žvirblis T et al. Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience. Acta Med Litu 2016; 23 (1): 24–34. doi: 10.6001/actamedica.v23i1.3267.

9. Petrelli F, Coinu A, Cabiddu M et al. KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials. Med Oncol 2013; 30 (3): 650. doi: 10.1007/s12032-013-0650-4.

10. De Mattia E, Bignucolo A, Toffoli G et al. Genetic markers of the host to predict the efficacy of colorectal cancer targeted therapy. Curr Med Chem 2020; 27 (25): 4249–4273. doi: 10.2174/0929867326666190712151417.

11. Gaibar M, Galán M, Romero-Lorca A et al. Genetic variants of ANGPT1, CD39, FGF2 and MMP9 linked to clinical outcome of Bevacizumab plus chemotherapy for metastatic colorectal cancer. Int J Mol Sci 2021; 22 (3): 1381. doi: 10.3390/ijms22031381.

12. Qin W, Zhao B, Wang D et al. A genetic variant in CD274 is associated with prognosis in metastatic colorectal cancer patients treated with Bevacizumab-based chemotherapy. Front Oncol 2022; 12 : 922342. doi: 10.3389/fonc.2022.922342.

13. González-Vacarezza N, Alonso I, Arroyo G et al. Predictive biomarkers candidates for patients with metastatic colorectal cancer treated with bevacizumab-containing regimen. Drug Metab Pers Ther 2016; 31 (2): 83–90. doi: 10.1515/dmpt-2015-0027.

14. Jaworek H, Koudelakova V, Slavkovsky R et al. The absence of high-risk human papillomavirus in Czech non-small cell lung cancer cases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020; 164 (1): 71–76. doi: 10.5507/bp.2018.079.

15. The R project for statistical computing. [online]. Available from: https: //www.R-project.org/.

16. Commo F, Guinney J, Ferté C et al. rCGH: a comprehensive array-based genomic profile platform for precision medicine. Bioinformatics 2016; 32 (9): 1402–1404. doi: 10.1093/bioinformatics/btv718.

17. Mermel CH, Schumacher SE, Hill B et al. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol 2011; 12 (4): R41. doi: 10.1186/gb-2011-12-4-r41.

18. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37 (1): 1–13. doi: 10.1093/nar/gkn923.

19. Lang L, Loveless R, Teng Y. Emerging links between control of mitochondrial protein ATAD3A and cancer. Int J Mol Sci 2020; 21 (21): 7917. doi: 10.3390/ijms21217917.

20. Zhang T, Nie Y, Gu J et al. Identification of mitochondrial-related prognostic biomarkers associated with primary bile acid biosynthesis and tumor microenvironment of hepatocellular carcinoma. Front Oncol 2021; 11 : 587479. doi: 10.3389/fonc.2021.587479.

21. Hubstenberger A, Labourdette G, Baudier J et al. ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human glioma cell lines and present in vitro anti-oncogenic and chemoresistant properties. Exp Cell Res 2008; 314 (15): 2870–2883. doi: 10.1016/j.yexcr.2008.06.017.

22. Zhu Z, Fu H, Wang S et al. Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer. Ann Transl Med 2020; 8 (22): 1484. doi: 10.21037/atm-20-6620.

23. Ovaska K, Matarese F, Grote K et al. Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer. PLoS Comput Biol 2013; 9 (6): e1003100. doi: 10.1371/journal.pcbi.1003100.

24. Huang KH, Chow KC, Chang HW et al. ATPase family AAA domain containing 3A is an anti-apoptotic factor and a secretion regulator of PSA in prostate cancer. Int J Mol Med 2011; 28 (1): 9–15. doi: 10.3892/ijmm.2011.670.

25. Stringer SE. The role of heparan sulphate proteoglycans in angiogenesis. Biochem Soc Trans 2006; 34 (Pt 3): 451–453. doi: 10.1042/BST0340451.

26. Peixoto A, Relvas-Santos M, Azevedo R et al. Protein glycosylation and tumor microenvironment alterations driving cancer hallmarks. Front Oncol 2019; 9 : 380. doi: 10.3389/fonc.2019.00380.

27. Batmunkh E, Tátrai P, Szabó E et al. Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 2007; 38 (10): 1508–1515. doi: 10.1016/j.humpath.2007.02.017.

28. Kawahara R, Granato DC, Carnielli CM et al. Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma. PLoS One 2014; 9 (12): e115004. doi: 10.1371/journal.pone.0115004.

29. Xu R, Hu J. The role of JNK in prostate cancer progression and therapeutic strategies. Biomed Pharmacother 2020; 121 : 109679. doi: 10.1016/j.biopha.2019.109679.

30. Shimada K, Nakamura M, Ishida E et al. C-Jun NH2 terminal kinase activation and decreased expression of mitogen-activated protein kinase phosphatase-1 play important roles in invasion and angiogenesis of urothelial carcinomas. Am J Pathol 2007; 171 (3): 1003–1012. doi: 10.2353/ajpath.2007.070010.

31. Yang YM, Bost F, Charbono W et al. C-Jun NH (2) -terminal kinase mediates proliferation and tumor growth of human prostate carcinoma. Clin Cancer Res 2003; 9 (1): 391–401.

32. Wang J, Kuiatse I, Lee AV et al. Sustained c-Jun-NH2-kinase activity promotes epithelial-mesenchymal transition, invasion, and survival of breast cancer cells by regulating extracellular signal-regulated kinase activation. Mol Cancer Res 2010; 8 (2): 266–277. doi: 10.1158/1541-7786.MCR-09-0221.

33. Sharma M, Castro-Piedras I, Rodgers AD et al. Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer. Genes Cancer 2021; 12 : 77–95. doi: 10.18632/genesandcancer.217.

34. Nagahata T, Shimada T, Harada A et al. Amplification, up-regulation and over-expression of DVL-1, the human counterpart of the Drosophila disheveled gene, in primary breast cancers. Cancer Sci 2003; 94 (6): 515–518. doi: 10.1111/j.1349-7006.2003.tb01475.x.

35. Huang MY, Yen LC, Liu HC et al. Significant overexpression of DVL1 in Taiwanese colorectal cancer patients with liver metastasis. Int J Mol Sci 2013; 14 (10): 20492–20507. doi: 10.3390/ijms141020492.

36. Song P, Sekhon HS, Fu XW et al. Activated cholinergic signaling provides a target in squamous cell lung carcinoma. Cancer Res 2008; 68 (12): 4693–4700. doi: 10.1158/0008-5472.CAN-08-0183.

37. Schulten HJ, Hussein D, Al-Adwani F et al. Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma. Am J Cancer Res 2016; 6 (10): 2140–2161.

38. Caputo M, Frontini M, Velez-Cruz R et al. The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth. DNA Repair (Amst) 2013; 12 (4): 293–299. doi: 10.1016/j.dnarep.2013.01.008.

39. Domínguez-Sánchez MS, Sáez C, Japón MA et al. Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers. BMC Cancer 2011; 11 : 77. doi: 10.1186/1471-2407-11-77.

40. Li Y, Lin AW, Zhang X et al. Cancer cells and normal cells differ in their requirements for Thoc1. Cancer Res 2007; 67 (14): 6657–6664. doi: 10.1158/0008-5472.CAN-06-3234.

41. Liu C, Yue B, Yuan C et al. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer. Biochem Biophys Res Commun 2015; 468 (1–2): 53–58. doi: 10.1016/j.bbrc.2015.10.166.

42. Huang YC, Lin JM, Lin HJ et al. Genome-wide association study of diabetic retinopathy in a Taiwanese population. Ophthalmology 2011; 118 (4): 642–648. doi: 10.1016/j.ophtha.2010.07.020.

43. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer 2005; 5 (1): 29–41. doi: 10.1038/nrc1527.

44. Danguy A, Camby I, Kiss R. Galectins and cancer. Biochim Biophys Acta 2002; 1572 (2–3): 285–293. doi: 10.1016/s0304-4165 (02) 00315-x.

45. Guda MR, Tsung AJ, Asuthkar S et al. Galectin-1 activates carbonic anhydrase IX and modulates glioma metabolism. Cell Death Dis 2022; 13 (6): 574. doi: 10.1038/s41419-022-05024-z.

46. Ågesen TH, Berg M, Clancy T et al. CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early -⁠ and late-onset colorectal cancer. Genes Immun 2011; 12 (8): 653–662. doi: 10.1038/gene. 2011.43.

47. De Re V, Simula MP, Cannizzaro R et al. Galectin-10, eosinophils, and celiac disease. Ann N Y Acad Sci 2009; 1173 : 357–364. doi: 10.1111/j.1749-6632.2009.04627.x.

48. Than NG, Romero R, Xu Y et al. Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia. Placenta 2014; 35 (11): 855–865. doi: 10.1016/j.placenta.2014.07.015.

49. Gadde R, Cd D, Sheela SR. Placental protein 13: an important biological protein in preeclampsia. J Circ Biomark 2018; 7 : 1849454418786159. doi: 10.1177/1849454418786159.

50. Satelli A, Rao PS, Thirumala S et al. Galectin-4 functions as a tumor suppressor of human colorectal cancer. Int J Cancer 2011; 129 (4): 799–809. doi: 10.1002/ijc.25750.

51. Barrow H, Rhodes JM, Yu LG. Simultaneous determination of serum galectin-3 and -4 levels detects metastases in colorectal cancer patients. Cell Oncol (Dordr) 2013; 36 (1): 9–13. doi: 10.1007/s13402-012-0109-1.

52. Acharjee A, Agarwal P, Nash K et al. Immune infiltration and prognostic and diagnostic use of LGALS4 in colon adenocarcinoma and bladder urothelial carcinoma. Am J Transl Res 2021; 13 (10): 11353–11363.

53. Chen C, Duckworth CA, Fu B et al. Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis. Br J Cancer 2014; 110 (3): 741–752. doi: 10.1038/bjc.2013.793.

54. Li M, Liu X, Zhou Y et al. Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses. J Leukoc Biol 2009; 86 (1): 23–32. doi: 10.1189/jlb.1208761.

55. Swider A, Siegel R, Eskdale J et al. Regulation of interferon lambda-1 (IFNL1/IFN-l1/IL-29) expression in human colon epithelial cells. Cytokine 2014; 65 (1): 17–23. doi: 10.1016/j.cyto.2013.09.020.

56. An Y, Cai B, Chen J et al. MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2. Cancer Lett 2013; 329 (2): 228–235. doi: 10.1016/j.canlet.2012.11.005.

57. Wang H, Song X, Logsdon C et al. Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer. Cancer Res 2009; 69 (3): 1063–1070. doi: 10.1158/0008-5472.CAN-08-1751.

58. Yang HS, Matthews CP, Clair T et al. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Mol Cell Biol 2006; 26 (4): 1297–1306. doi: 10.1128/MCB.26.4.1297-1306.2006.

59. Lee HH, Son YJ, Lee WH et al. Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer. Int J Cancer 2010; 126 (8): 1817–1827. doi: 10.1002/ijc.24847.

60. Cha HJ, Lee HH, Chae SW et al. Tristetraprolin downregulates the expression of both VEGF and COX-2 in human colon cancer. Hepatogastroenterology 2011; 58 (107–108): 790–795.

61. Rounbehler RJ, Fallahi M, Yang C et al. Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state. Cell 2012; 150 (3): 563–574. doi: 10.1016/j.cell.2012.06.033.

62. Amoroso MR, Matassa DS, Laudiero G et al. TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins. Cell Death Differ 2012; 19 (4): 592–604. doi: 10.1038/cdd.2011.128.

63. Lee KS, Kwak Y, Nam KH et al. c-MYC copy-number gain is an independent prognostic factor in patients with colorectal cancer. PLoS One 2015; 10 (10): e0139727. doi: 10.1371/journal.pone.0139727.

64. Huang YH, Lin PC, Su WC et al. Association between altered oncogenic signaling pathways and overall survival of patients with metastatic colorectal cancer. Diag -⁠ nostics (Basel) 2021; 11 (12): 2308. doi: 10.3390/diagnostics11122308.

65. Seo KS, Park JH, Heo JY et al. SIRT2 regulates tumour hypoxia response by promoting HIF-1a hydroxylation. Oncogene 2015; 34 (11): 1354–1362. doi: 10.1038/ onc.2014.76.

66. Okino K, Nagai H, Hatta M et al. Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma. Oncol Rep 2003; 10 (5): 1219–1223. doi: 10.3892/or.10.5.1219.

67. Mizutani K, Miyamoto S, Nagahata T et al. Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer. Tumori 2005; 91 (6): 546–551. doi: 10.1177/030 089160509100616.

68. Iorio J, Lastraioli E, Tofani L et al. hERG1 and HIF-2a behave as biomarkers of positive response to Bevacizumab in metastatic colorectal cancer patients. Transl Oncol 2020; 13 (3): 100740. doi: 10.1016/j.tranon.2020. 01.001.

69. Lastraioli E, Bencini L, Bianchini E et al. hERG1 channels and glut-1 as independent prognostic indicators of worse outcome in stage I and II colorectal cancer: a pilot study. Transl Oncol 2012; 5 (2): 105–112. doi: 10.1593/tlo.11250.

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