Correlation between EpCAM expression and clinicopathologic characteristics of colorectal cancer: a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Likang ^1,2 , JIANG Lei ^1,2 , WANG Jun ^1,2 , YU Jiaojiao ^1,2 , ZHOU Yongning ^1,3 ,  YAO Nan ^1,2

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, The First Hospital, Lanzhou University, Lanzhou 730000, P. R. China;
3. Department of Gastroenterology, The First Hospital, Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding?author：

YAO Nan, Email: Pro-YaoNan@163.com

Keywords：

colorectal cancer; epithelial cell adhesion molecule; clinicopathologic characteristic; meta-analysis

DOI：

10.7507/1007-9424.202009018

Video：

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Objective To systematicly evaluate expression of epithelial cell adhesion molecule (EpCAM) in colorectal cancer (CRC) and its correlation with clinicopathologic characteristics of patient with CRC.Methods PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, VIP, and other databases were searched comprehensively. The retrieved literatures were imported into Endnote X9. The data about the expression of EpCAM in the CRC and the relationship between EpCAM expression and clinicopathologic characteristics of patients with CRC were screened and extracted. RevMan 5.3 software was used for meta-analysis.Results A total of 5 396 patients with CRC were included. The meta-analysis results showed that the expression rate of EpCAM in the CRC tissues or blood was significantly higher than that in the benign colorectal tumor and normal tissue or blood (P<0.05). The high expression rates of EpCAM in the Dukes C+D stage, tumor diameter >3 cm, infiltration state of tumor margin, with lymph node and distant metastasis of the CRC were significantly higher than those in the A+B stage, tumor diameter ≤3 cm, dilated state of tumor margin, without lymph node and distant metastasis (P<0.05).Conclusion Results of this meta-analysis suggest that expression of EpCAM might be related to some clinicopathologic characteristics (carcinogenesis, Dukes stage, tumor size, tumor margin morphology, lymph node metastasis, distant metastasis) of patients with CRC.

Citation： WANG Likang, JIANG Lei, WANG Jun, YU Jiaojiao, ZHOU Yongning, YAO Nan. Correlation between EpCAM expression and clinicopathologic characteristics of colorectal cancer: a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(5): 571-579. doi: 10.7507/1007-9424.202009018 Copy

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2.	Herlyn M, Steplewski Z, Herlyn D, et al. Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc Natl Acad Sci USA, 1979, 76(3): 1438-1442.
3.	Trzpis M, McLaughlin PM, de Leij LM, et al. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol, 2007, 171(2): 386-395.
4.	McDougall AR, Tolcos M, Hooper SB, et al. Trop2: from development to disease. Dev Dyn, 2015, 244(2): 99-109.
5.	Varga M, Obrist P, Schneeberger S, et al. Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res, 2004, 10(9): 3131-3136.
6.	Schmidt M, Scheulen ME, Dittrich C, et al. An open-label, randomized phase Ⅱ study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol, 2010, 21(2): 275-282.
7.	Battista MJ, Cotarelo C, Jakobi S, et al. Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients. J Cancer Res Clin Oncol, 2014, 140(7): 1097-1102.
8.	張子志. 免疫組織化學 SP 法測定原發性結直腸癌組織中 ESA 和 CD44 蛋白表達的關系及臨床病理意義分析. 中國實用醫刊, 2016, 43(22): 27-30.
9.	吳迪, 蘇琪, 殷紅專, 等. 上皮特異性抗原和 CD44 蛋白在原發性結直腸癌組織中的表達及臨床意義. 醫學綜述, 2016, 22(21): 4332-4334, 4338.
10.	Kim JH, Bae JM, Song YS, et al. Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma. Oncotarget, 2016, 7(12): 13372-13387.
11.	Rupp AK, Rupp C, Keller S, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol, 2011, 122(2): 437-446.
12.	張秋菊, 劉斌, 邢傳平, 等. 結直腸癌組織中 ESA 和 CD44 的表達及其臨床病理意義. 世界華人消化雜志, 2009, 17(14): 1417-1421.
13.	Lugli A, Iezzi G, Hostettler I, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer, 2010, 103(3): 382-390.
14.	Kim JH, Bae JM, Kim KJ, et al. Differential features of microsatellite-unstable colorectal carcinomas depending on EPCAM expression status. Korean J Pathol, 2014, 48(4): 276-282.
15.	Karanikiotis C, Skiadas I, Karina M, et al. A novel chromatographic method for Ep-CAM mRNA detection in peripheral blood and bone marrow of patients with metastatic colorectal cancer. Anticancer Res, 2005, 25(1A): 319-323.
16.	Went P, Vasei M, Bubendorf L, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer, 2006, 94(1): 128-135.
17.	Kuhn S, Koch M, Nübel T, et al. A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. Mol Cancer Res, 2007, 5(6): 553-567.
18.	Gosens MJ, van Kempen LC, van de Velde CJ, et al. Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol, 2007, 20(2): 221-232.
19.	Paret C, Hildebrand D, Weitz J, et al. C4.4A as a candidate marker in the diagnosis of colorectal cancer. Br J Cancer, 2007, 97(8): 1146-1156.
20.	Dhayat S, Sorescu S, Vallb?hmer D, et al. Prognostic significance of EpCAM-positive disseminated tumor cells in rectal cancer patients with stage Ⅰ disease. Am J Surg Pathol, 2012, 36(12): 1809-1816.
21.	Goossens-Beumer IJ, Zeestraten EC, Benard A, et al. Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer. Br J Cancer, 2014, 110(12): 2935-2944.
22.	Chai XB, Song RF, Xu F. Expression changes in epithelial cell adhesion molecule during colorectal cancer tumorigenesis. Genet Mol Res, 2015, 14(3): 7624-7629.
23.	Zhou FQ, Qi YM, Xu H, et al. Expression of EpCAM and Wnt/ β-catenin in human colon cancer. Genet Mol Res, 2015, 14(2): 4485-4494.
24.	Seeber A, Untergasser G, Spizzo G, et al. Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer. Int J Cancer, 2016, 139(3): 657-663.
25.	Akolkar D, Patil D, Crook T, et al. Circulating ensembles of tumor-associated cells: A redoubtable new systemic hallmark of cancer. Int J Cancer, 2020, 146(12): 3485-3494.
26.	Münz M, Kieu C, Mack B, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene, 2004, 23(34): 5748-5758.

1. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet, 2019, 394(10207): 1467-1480.
2. Herlyn M, Steplewski Z, Herlyn D, et al. Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc Natl Acad Sci USA, 1979, 76(3): 1438-1442.
3. Trzpis M, McLaughlin PM, de Leij LM, et al. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol, 2007, 171(2): 386-395.
4. McDougall AR, Tolcos M, Hooper SB, et al. Trop2: from development to disease. Dev Dyn, 2015, 244(2): 99-109.
5. Varga M, Obrist P, Schneeberger S, et al. Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res, 2004, 10(9): 3131-3136.
6. Schmidt M, Scheulen ME, Dittrich C, et al. An open-label, randomized phase Ⅱ study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol, 2010, 21(2): 275-282.
7. Battista MJ, Cotarelo C, Jakobi S, et al. Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients. J Cancer Res Clin Oncol, 2014, 140(7): 1097-1102.
8. 張子志. 免疫組織化學 SP 法測定原發性結直腸癌組織中 ESA 和 CD44 蛋白表達的關系及臨床病理意義分析. 中國實用醫刊, 2016, 43(22): 27-30.
9. 吳迪, 蘇琪, 殷紅專, 等. 上皮特異性抗原和 CD44 蛋白在原發性結直腸癌組織中的表達及臨床意義. 醫學綜述, 2016, 22(21): 4332-4334, 4338.
10. Kim JH, Bae JM, Song YS, et al. Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma. Oncotarget, 2016, 7(12): 13372-13387.
11. Rupp AK, Rupp C, Keller S, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol, 2011, 122(2): 437-446.
12. 張秋菊, 劉斌, 邢傳平, 等. 結直腸癌組織中 ESA 和 CD44 的表達及其臨床病理意義. 世界華人消化雜志, 2009, 17(14): 1417-1421.
13. Lugli A, Iezzi G, Hostettler I, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer, 2010, 103(3): 382-390.
14. Kim JH, Bae JM, Kim KJ, et al. Differential features of microsatellite-unstable colorectal carcinomas depending on EPCAM expression status. Korean J Pathol, 2014, 48(4): 276-282.
15. Karanikiotis C, Skiadas I, Karina M, et al. A novel chromatographic method for Ep-CAM mRNA detection in peripheral blood and bone marrow of patients with metastatic colorectal cancer. Anticancer Res, 2005, 25(1A): 319-323.
16. Went P, Vasei M, Bubendorf L, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer, 2006, 94(1): 128-135.
17. Kuhn S, Koch M, Nübel T, et al. A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. Mol Cancer Res, 2007, 5(6): 553-567.
18. Gosens MJ, van Kempen LC, van de Velde CJ, et al. Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol, 2007, 20(2): 221-232.
19. Paret C, Hildebrand D, Weitz J, et al. C4.4A as a candidate marker in the diagnosis of colorectal cancer. Br J Cancer, 2007, 97(8): 1146-1156.
20. Dhayat S, Sorescu S, Vallb?hmer D, et al. Prognostic significance of EpCAM-positive disseminated tumor cells in rectal cancer patients with stage Ⅰ disease. Am J Surg Pathol, 2012, 36(12): 1809-1816.
21. Goossens-Beumer IJ, Zeestraten EC, Benard A, et al. Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer. Br J Cancer, 2014, 110(12): 2935-2944.
22. Chai XB, Song RF, Xu F. Expression changes in epithelial cell adhesion molecule during colorectal cancer tumorigenesis. Genet Mol Res, 2015, 14(3): 7624-7629.
23. Zhou FQ, Qi YM, Xu H, et al. Expression of EpCAM and Wnt/ β-catenin in human colon cancer. Genet Mol Res, 2015, 14(2): 4485-4494.
24. Seeber A, Untergasser G, Spizzo G, et al. Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer. Int J Cancer, 2016, 139(3): 657-663.
25. Akolkar D, Patil D, Crook T, et al. Circulating ensembles of tumor-associated cells: A redoubtable new systemic hallmark of cancer. Int J Cancer, 2020, 146(12): 3485-3494.
26. Münz M, Kieu C, Mack B, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene, 2004, 23(34): 5748-5758.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Correlation between EpCAM expression and clinicopathologic characteristics of colorectal cancer: a meta-analysis

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