Kolorektal Kanserlerin Tanı ve Prognostik Takibinde Eski ve Yeni Serum Biyobelirteçleri: Sistematik İnceleme ve Meta-Analiz

Öz

Bu mini derleme ve sistematik meta analizde kolorektal karsinomun tanısında ya da prognozunda araştırılmış olan bazı biyobelirteçlerin irdelenmesi amaçlanmıştır. Yapılan analizler karsinoembriyonik antijenin (CEA) kolorektal karsinom tanısında orta duyarlılık ve yüksek özgüllük değerlerinde olduğunu, ancak kolorektal kanseri yakalamakta yetersiz olduğunu, prognozun belirlenmesinde kullanılabileceğini göstermektedir. Karbonhidrat Antijeni 19-9’un (CA19-9) tek başına kolorektal karsinom taramasında, tanısında, prognozunun belirlenmesinde veya nükslerin yakalanmasında kullanılamayacağı, diğer belirteçlerle birlikte kullanıldığında bilgi sağlayıcı olabileceği görülmüştür. Kanser Antijeni 242’nin (CA242) kolorektal karsinom tanısında ve prognozunun belirlenmesinde özellikle CEA ve/veya CA19-9 gibi farklı tümör belirteçleriyle birlikte kullanılabileceği gösterilmiştir. C-reaktif Proteininin (CRP) inflamasyon için spesifik bir belirteç olduğu, kolorektal karsinom gelişme riskini belirlemede, tanı koymada ve prognozu anlamada kullanılabileceğini ancak kolorektal karsinoma özgül bir belirteç olmadığı görülmüştür. Vasküler Endotelyal Büyüme Faktörü (VEGF) ile kolorektal karsinomun ilişkili olduğu ve VEGF’in bu olgularda tanıda ve prognozu belirlemede belirteç olarak kullanılabileceği ortaya konulmuştur. MicroRNA’ların kolorektal karsinom taramasında, tanısında ve prognozunun belirlenmesinde kullanılabileceği gösterilmiştir. Diğer belirteçlerden Kanser Antijeni 50 (CA-50), İnsülin Benzeri Büyüme Faktörü Bağlanma Proteini 3 (IGFBP-3),  İnsülin Benzeri Büyüme Faktörü-1’i (IGF-1), Kanser Antijeni 72-4’ün (CA72-4), Tümör İlişkili Glikoprotein-72 (TAG-72), P53, Kanser Antijeni 125’in (CA125), c-erbB-2 proteini, Doku Metalloproteinaz İnhibitörü-1’in (TIMP-1) ve Pirüvat Kinaz İzoenzimi M2’nin (M2-PK) kolorektal karsinomda sınırlı oranda kullanılabileceği görülmüştür. Kolorektal karsinomların taranmasında, tanısında, izleminde ve prognozunun belirlenmesinde ileri derecede güvenilir bir biyobelirteç henüz belirlenebilmiş değildir. Ancak belirteçlerin araştırılması değişik duyarlılık ve özgüllük oranlarına rağmen klinisyen ve hasta için büyük fayda sağlamaktadır. Özellikle bazı belirteçlerin kombine kullanımının bu olgularda önemli yarar sağladığı görülmüştür.

Anahtar Kelimeler

• Kolorektal karsinom,CEA,CA19-9,CA242,microRNA,tanı,prognostik faktör

Former and Recent Serum Biomarkers in Diagnosis and Prognostic Follow-up of Colorectal Cancers: Systematic Review and Meta-Analysis

Öz

This mini review and systematic meta-analysis aimed to investigate some biomarkers that have been investigated in the diagnosis or prognosis of colorectal carcinoma. Analyzes show that carcinoembryonic antigen (CEA) has moderate sensitivity and high specificity in the diagnosis of colorectal carcinoma, but it is insufficient to detect colorectal cancer and can be used to determine prognosis. Carbohydrate Antigen 19-9 (CA19-9) alone cannot be used for colorectal carcinoma screening, diagnosis, prognosis or detection of relapses, and it can be used when used in conjunction with other markers. It has been shown that Cancer Antigen 242 (CA242) can be used in combination with different tumor markers such as CEA and / or CA19-9 in the diagnosis and prognosis of colorectal carcinoma. C-reactive protein (CRP) is a specific marker for inflammation, it can be used to determine the risk of developing colorectal carcinoma, to diagnose and to understand prognosis, but it is not a specific marker of colorectal carcinoma. Vascular Endothelial Growth Factor (VEGF) is associated with colorectal carcinoma and VEGF can be used as a marker in the diagnosis and prognosis of these cases. It has been shown that microRNAs can be used for colorectal carcinoma screening, diagnosis and prognosis. Other markers include Cancer Antigen 50 (CA-50), Insulin Like Growth Factor Binding Protein 3 (IGFBP-3), Insulin Like Growth Factor-1 (IGF-1), Cancer Antigen 72-4 (CA72-4). Tumor Related Glycoprotein-72 (TAG-72), P53, Cancer Antigen 125 (CA125), c-erbB-2 protein, Tissue Metalloproteinase Inhibitor-1 (TIMP-1) and Pyruvate Kinase Isoenzyme M2 (M2-PK) have been shown to be limited in colorectal carcinoma. A highly reliable biomarker for screening, diagnosis, follow-up and prognosis of colorectal carcinomas has not yet been established. However, the search for markers is of great benefit to the clinician and the patient, despite varying sensitivity and specificity rates. In particular, the combined use of some markers has been shown to provide significant benefit in these cases.

Anahtar Kelimeler

• Colorectal carcinoma,CEA,Ca19-9,CA 242,Micro RNA,prognostic factor

Kaynakça

1. Liu Z, Zhang Y, Niu Y, et al. A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer. Plos One. 2014;9(8):e103910. doi: 10.1371/journal.pone.0103910.
2. Duffy MJ, van Dalen A, Haglund C, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. European Journal of Cancer. 2007;43(9):1348-60.
3. Bray C, Bell LN, Liang H, Collins D, Yale SH. Colorectal cancer screening. Wisconsin Medical Journal. 2017;116(1):27-33.
4. Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: Is it clinically useful? Clinical Chemistry. 2001;47(4):624-30.
5. Issa IA, Noureddine M. Colorectal cancer screening: An updated review of the available options. World Journal of Gastroenterolgy. 2017;23(28):5086-5096. doi: 10.3748/wjg.v23.i28.5086.
6. Onyoh EF, Hsu WF, Chang LC, Lee YC, Wu MS, Chiu HM. The rise of colorectal cancer in Asia: epidemiology, screening, and management. Current Gastroenterology Reports. 2019;21(8):36. doi: 10.1007/s11894-019-0703-8.
7. Peng Q, Shen Y, Lin K, Zou L, Shen Y, Zhu Y. Identification of microRNA-92a and the related combination biomarkers as promising substrates in predicting risk, recurrence and poor survival of colorectal cancer. Journal of Cancer. 2019;10(14):3154-3171. doi: 10.7150/jca.30306.
8. Wei C, Lei L, Hui H, Tao Z. MicroRNA-124 regulates TRAF6 expression and functions as an independent prognostic factor in colorectal cancer. Oncology Letters. 2019;18(1):856-863. doi: 10.3892/ol.2019.10358.

9. Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Investigation. 2005;23(4):338-51.
10. Fernandes LC, Kim SB, Matos D. Cytokeratins and carcinoembryonic antigen in diagnosis, staging and prognosis of colorectal adenocarcinoma. World Journal of Gastroenterology. 2005;11(5):645-8.
11. Fletcher RH. Carcinoembryonic antigen. Annals of Internal Medicine, 1986;104:66–73.
12. Klapdor R, Aronsson A-C, Duffy MJ, et al. Tumor markers in gastrointestinal cancers: European Group on Tumour Markers (EGTM) recommendations. Anticancer Research. 1999;119:2811–2815.
13. Duffy MJ, van Dalen A, Haglund C, et al. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. European Journal of Cancer. 2003;39(6):718-27.
14. Duffy MJ. CA 19-9 as a marker for gastrointestinal cancers: a review. Annals of Clinical Biochemistry. 1998;35(3):364-70.
15. Midgley R, Kerr D. Colorectal cancer. Lancet. 1999;353:391–9.
16. Wild N, Andres H, Rollinger W, et al. A combination of serum markers for the early detection of colorectal cancer. Clinical Cancer Research. 2015;16(24):6111-21. doi: 10.1158/1078-0432.CCR-10-0119.
17. Lee H, Rhee H, Kang HJ, et al. Macrophage migration inhibitory factor may be used as an early diagnostic marker in colorectal carcinomas. America Journal of Clinical Pathology. 2008;129(5):772-9. doi: 10.1309/GFCLLRH8A68XKMJN.
18. Saito N, Kameoka S. Serum laminin is an independent prognostic factor in colorectal cancer. International Journal of Colorectal Dissease. 2005;20(3):238-44.
19. Marrelli D, Caruso S, Neri A, et al. Clinical utility of serum tumor markers in the diagnosis of malignant intestinal occlusion. A prospective observational study. The International Journal of Biological Markers. 2011;26(1):58-64.
20. Dbouk HA, Tawil A, Nasr F, Kandakarjian L, Abou-Merhi R. Significance of CEA and VEGF as diagnostic markers of colorectal cancer in Lebanese patients. The Open Clinical Cancer Journal. 2007;8(1):1-5. doi: 10.2174/1874189400701010001.
21. Chen JS, Chou YP, Chen KT, et al. Detection of annexin A autoantibodies in sera from colorectal cancer patients. Journal of Clinical Gastroenterology. 2011;45(2):125-32. doi: 10.1097/MCG.0b013e3181e880ee.
22. Takeda A, Otani Y, Iseki H, et al. Clinical significance of large tenascin-C spliced variant as a potential biomarker for colorectal cancer. World Journal of Surgery. 2007;31(2):388-94.
23. Coban S, Ozkan H, Köklü S, et al. The utility of serum receptor-binding cancer antigen expressed on SiSo cells in gastrointestinal tract cancers. Canadian Journal of Gastroenterology. 2006;20(9):593-6. doi: 10.1155/2006/276247
24. Bast RC Jr, Ravdin P, Hayes DF, et al. American Society of Clinical Oncology Tumor Markers Expert Panel. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. Journal of Clinical Oncology. 2001;19(6):1865-78.
25. Grem J. The prognostic importance of tumor markers in adenocarcinomas of the gastrointestinal tract. Current Opinion in Oncology. 1997;9(4):380-7.
26. Huo YR, Glenn D, Liauw W, Power M, Zhao J, Morris DL. Evaluation of carcinoembryonic antigen (CEA) density as a prognostic factor for percutaneous ablation of pulmonary colorectal metastases. European Radiology. 2017;27(1):128-137.
27. Peltonen R, Österlund P, Lempinen M, Nordin A, Stenman UH, Isoniemi H. Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases. Tumour Biology. 2018;40(1):1-9. doi: 10.1177/1010428317752944.
28. Yang KM, Park IJ, Kim CW, Roh SA, Cho DH, Kim JC. The prognostic significance and treatment modality for elevated pre- and postoperative serum CEA in colorectal cancer patients. Annals of Surgical Treatment and Research. 2016;91(4):165-171.
29. Park IJ, Choi GS, Lim KH, Kang BM, Jun SH. Serum carcinoembryonic antigen monitoring after curative resection for colorectal cancer: clinical significance of the preoperative level. Annals of Surgical Oncology. 2009;16(11):3087-93. doi: 10.1245/s10434-009-0625-z.
30. Louhimo J, Carpelan HM, Alfthan H, Stenman UH, Järvinen HJ, Haglund C. Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. International Journal of Cancer. 2002;101(6):545-8.
31. Carriquiry LA, Pineyro A. Should carcinoembryonic antigen be used in the management of patients with colorectal cancer. Dissease of Colon Rectum. 1999;42:921–9.
32. Carpelan HM, Louhimo J, Stenman UH, Alfthan H, Haglund C. CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers. Anticancer Research. 2002;22(4):2311-6.
33. Nakayama T, Watanabe M, Teramoto T, Kitajima M. CA19-9 as a predictor of recurrence in patients with colorectal cancer. Journal of Surgical Oncology. 1997;66(4):238-43.
34. Okamura R, Hasegawa S, Hida K, et al. Japanese study group for postoperative follow-up of colorectal cancer. The role of periodic serum CA19-9 test in surveillance after colorectal cancer surgery. International Journal of Clinical Oncology. 2017;22(1):96-101. doi: 10.1007/s10147-016-1027-4.
35. Wang J, Wang X, Yu F, et al. Combined detection of preoperative serum CEA, CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients. International Journal of Clinical and Experimental Pathology. 2015;8(11):14853-63.
36. Lindmark G, Bergström R, Påhlman L, Glimelius B. The association of preoperative serum tumour markers with Dukes' stage and survival in colorectal cancer. British Journal of Cancer. 1995;71(5):1090-4.
37. Behbehani AI, Al-Sayer H, Farghaly M, et al. Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait. International Journal of Biological Markers. 2000;15(1):51-5.
38. Filella X, Molina R, Piqué JM, et al. Use of CA 19-9 in the early detection of recurrences in colorectal cancer: comparison with CEA. Tumour Biology. 1994;15(1):1-6.
39. Dou H, Sun G, Zhang L. CA242 as a biomarker for pancreatic cancer and other diseases. Progress in Molecular Biology and Translational Science. 2019;162:229-239. doi: 10.1016/bs.pmbts.2018.12.007.
40. Wu J, Yu H, Shao Y. Significance of CEA and CA242 in the diagnosis of colorectalcarcinoma. Zhonghua Zhong Liu Za Zhi. 1995;17(6):438-40.
41. Yang XQ, Chen C, Hou JX, Peng CW, Huang CQ, Li Y. Preoperative serum carbohydrate antigen 242 is a useful predictive and prognostic marker in colorectal cancer. Hepatogastroenterology. 2011;58(106):377-82.
42. Pathak A, Agrawal A. Evolution of C-Reactive Protein. Front Immunology. 2019;30(10):943. doi: 10.3389/fimmu.2019.00943.
43. Pathak S, Nunes QM, Daniels IR, Smart NJ. Is C-reactive protein useful in prognostication for colorectalcancer? A systematic review. Colorectal Dissease. 2014;16(10):769-76. doi: 10.1111/codi.12700.
44. Wu Y, Potempa LA, El Kebir D, Filep JG. C-reactive protein and inflammation: conformational changes affect function. Biological Chemistry. 2015;396(11):1181-97. doi: 10.1515/hsz-2015-0149.
45. Tsilidis KK, Branchini C, Guallar E, Helzlsouer KJ, Erlinger TP, Platz EA. C-reactive protein and colorectal cancer risk: a systematic review of prospective studies. International Journal of Cancer. 2008;123(5):1133-40. doi: 10.1002/ijc.23606.
46. Kigawa N, Budhathoki S, Yamaji T, Iwasaki M, Inoue M, Tsugane S. Association of plasma C-reactive protein level with the prevalence of colorectal adenoma: the colorectal adenoma study in Tokyo. Scientific Reports. 2017;7(1):4456. doi: 10.1038/s41598-017-04780-9.
47. Uccelli A, Wolff T, Valente P, et al. Vascular endothelial growth factor biology for regenerative angiogenesis. Swiss Medical Weekly. 2019;149:w20011. doi: 10.4414/smw.2019.20011.
48. Zhou LP, Luan H, Dong XH, Jin GJ, Man DL, Shang H. Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis. Genetics and Molecular Research. 2011;10(4):3674-88. doi: 10.4238/2011.October.31.13.
49. Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000;12:1232-1235.
50. Bae SJ, Kim JW, Kang H, et al. Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936 C>T) gene and colon cancer in Korea. Anticancer Res. 2008;28:1271-1276.
51. Wang Y, Yao X, Ge J, Hu F, Zhao Y. Can vascular endothelial growth factor and microvessel density be used as prognostic biomarkers for colorectal cancer? A systematic review and meta-analysis. Scientific World Journal. 2014;2014:1-13. doi: 10.1155/2014/102736.
52. Yau TO, Tang CM, Harriss EK, Dickins B, Polytarchou C. Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis. Scientific Reports. 2019;9(1):1-13. doi: 10.1038/s41598-019-45570-9.
53. Guraya S. Prognostic significance of circulating microRNA-21 expression in esophageal, pancreatic and colorectal cancers; a systematic review and meta-analysis. Int J Surg. 2018;60:41-47. doi: 10.1016/j.ijsu.2018.10.030.
54. Shan M, Tian Q, Zhang L. Serum CA50 levels in patients with cancers and other diseases. Progress in Molecular Biology and Translational Science. 2019;162:187-198. doi: 10.1016/bs.pmbts.2018.12.006.
55. Yoon YS, Keum N, Zhang X, Cho E, Giovannucci EL. Circulating levels of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio and colorectal adenomas: A meta-analysis. Cancer Epidemiology. 2015;39(6):1026-35. doi: 10.1016/j.canep.2015.09.004.
56. Yanqing H, Cheng D, Ling X. Serum CA72-4 as a Biomarker in the diagnosis of colorectal cancer: A meta-analysis. Open Med (Wars). 2018;13:164-171. doi: 10.1515/med-2018-0026.
57. Cho J, Kim KM, Kim HC, et al. The prognostic role of tumor associated glycoprotein 72 (TAG-72) in stage II and III colorectal adenocarcinoma. Pathol Res Pract. 2019;215(1):171-176. doi: 10.1016/j.prp.2018.10.024.
58. Teras LR, Gapstur SM, Maliniak ML, et al. Prediagnostic antibodies to serum p53 and subsequent colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2018;27(2):219-223. doi: 10.1158/1055-9965.EPI-17-0407.
59. Gao Y, Wang J, Zhou Y, Sheng S, Qian SY, Huo X. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 2018;8(1):2732. doi: 10.1038/s41598-018-21048-y.
60. McKay JA, Loane JF, Ross VG, et al. c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86(4):568-73.
61. Meng C, Yin X, Liu J, Tang K, Tang H, Liao J. TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis. PLoS One. 2018;13(11):e0207039. doi: 10.1371/journal.pone.0207039.
62. Uppara M, Adaba F, Askari A, et al. A systematic review and meta-analysis of the diagnostic accuracy of pyruvate kinase M2 isoenzymatic assay in diagnosing colorectal cancer. World J Surg Oncol. 2015;13:48-56. doi: 10.1186/s12957-015-0446-4.