EpCAM EXPRESSION IN BREAST TUMOR CELLS AND THEIR RELATION TO CLINICAL AND PATHOLOGICAL PARAMETERS AND MOLECULAR SUBTYPE OF CANCER
Keywords:
breast cancer, disease prognosis, EpCAM protein, molecular subtypeAbstract
Objective: to determine the features of EpCAM protein expression in samples of the breast cancer cells depending on the stage of the disease and the molecular subtype of the tumor. Object and method: specimens of the primary tumor in 35 patients with I–II stage of the breast cancer. Expression of EpCAM, Ki67, Her2/ neu, estrogen receptors (RE) and progesterone (RP) were determined by immunohistochemical method. EpCAM gene expression in samples of breast cancer was evaluated using Oncomine open-source bioinformatic analysis. Functional linkage analysis of the EpCAM protein was performed using a database and FunCoup algorithm. Statistical analysis was performed using GraphPadPrism7. Results: the highest (p = 0.0058) expression level of EpCAM protein was detected in cells of luminal A subtype of the breast cancer. Analysis of the samples grouped by stage showed an increase in the expression of EpCAM with disease progression (p = 0.0234). Analysis showed an inverse correlation between the expression level of EpCAM and the level of Ki67 proliferation marker: the lowest (p = 0.1088) expression of the latter was detected in the samples of the luminal A molecular subtype of the breast cancer. Conclusions: the highest (p = 0.0058) expression level of EpCAM protein was detected in cells of luminal A molecular subtype of the breast cancer. Analysis of the samples grouped by stage showed an increase in the expression of EpCAM with disease progression (p = 0.0234). The expression level of EpCAM shows an inverse correlation with the level of Ki67 proliferation marker: the lowest (p = 0.1088) expression of the latter was detected in the samples of the luminal A molecular subtype of the breast cancer.
References
Linnenbach AJ, Wojcierowski J, Wu SA, et al. Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733. Proc Natl Acad Sci USA 1989; 86 (1): 27–31.
Zhang D, Liu X, Gao J, et al. The role of epithelial cell adhesion molecule N-glycosylation on apoptosis in breast cancer cells. Tumour Biol 2017; 39 (3): 1010–34.
Litvinov SV, Bakker HA, Gourevitch MM, et al. Evidence for a role of the epithelial glycoprotein 40 (Ep-CAM) in epithelial cell-cell adhesion. Cell Adhes Commun 1994; 2 (5): 417–28.
Liu X, Gao J, Sun Y, et al. Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. Biol Chem 2017; 398 (10): 1119–26.
Balzar M, Winter MJ, de Boer CJ, Litvinov SV. The biology of the 17–1A antigen (Ep-CAM). J Mol Med 1999; 77 (10): 699–712.
Casaletto JB, Geddie ML, Abu-Yousif AO, et al. MM-131, a bispecific anti-Met/EpCAM mAb, inhibits HGF-dependent and HGF-independent Met signaling through concurrent binding to EpCAM. Proc Natl Acad Sci USA 2019; 116 (15): 7533–42.
Kuan II, Lee CC, Chen CH, et al. The extracellular domain of epithelial cell adhesion molecule (EpCAM) enhances multipotency of mesenchymal stem cells through EGFR-LIN28-LET7 signaling. J Biol Chem 2019; 294 (19): 7769–86.
Carneiro FP, Muniz-Junqueira MI, Carneiro MV, et al. Anti-EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash. Oncol Lett 2019; 18 (2): 2019–24.
Pauli C, Munz M, Kieu C, et al. Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas. Cancer Lett 2003; 193 (1): 25–32.
Baeuerle PA. Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer 2007; 96 (3): 417–23.
Osta WA, Chen Y, Mikhitarian K, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 2004; 64 (16): 5818–24.
Wen KC, Sung PL, Chou YT, et al. The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma. Gynecol Oncol 2018; 148 (2): 383–392.
Heideman DA, Snijders PJ, Craanen ME, et al. Selective gene delivery toward gastric and sophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors Cancer Gene Ther 2001; 8 (5): 342–51.
Fong D, Steurer M, Obrist P, et al. Ep-CAM expression in pancreatic and ampullarycarcinomas: frequency and prognostic relevance. J Clin Pathol 2008; 61: 31–35.
Dhayat S, Sorescu S, Vallböhmer 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): 1809–16.
Varga M, Obrist P, Schneeberger S, et al. Overexpression of epithelial cell adhesionmolecule antigen in gallbladder carcinoma is an independent marker for poor survival.Clin Cancer Res 2004; 10: 3131–36.
Spizzo G, Went P, Dirnhofer S, et al. Overexpression of epithelial cell adhesionmolecule (Ep-CAM) is an independent prognostic marker for reduced survival ofpatients with epithelial ovarian cancer. Gynecol Oncol 2006; 10: 483–88.
Maetzel D, Denzel S, Mack B, et al. Nuclear signalling by tumour-associated antigenEpCAM. Nat Cell Biol 2009; 11: 61–71.
Gao J, Liu X, Yang F et al. By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis. Oncotarget 2015: 6 (29): 27187–98.
Gong Y, Liu YR, Ji P, et al. Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study. Sci Rep 2017; 27 (7): 45411–21.
Prado-Vázquez G, Gámez-Pozo A, Trilla-Fuertes L, et al. A novel approach to triple-negative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses. Sci Rep 2019; 9 (1): 1538–50.
Prat A, Pineda E, Adamo B, et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast 2015; 24: 26–35.
Jiang Z, Deng T, Jones R, et al. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J Clin Invest 2010; 120 (9): 3296–309.
Shulman M, Wilde CD, Kohler G. A better cell line for making hybridomas secreting specific antibodies. Nature 1978; 276: 269–70.
Munz M, Kieu C, Mack B, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 2004; 23 (34): 5748–58.
Spizzo G, Gastl G, Obrist P, et al. Methylation status of the Ep-CAM promoter regionin human breast cancer cell lines and breast cancer tissue. Cancer Lett 2007; 246: 253–61.
Chen Y, Liu L, Guo Z, et al. Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors. Oncol Lett 2019; 17 (2): 2047–56.
Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 2003; 100 (14): 8418–23.
Curtis C, Shah SP, Chin SF, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012; 486 (7403): 346–52.
Fan J, Tatum R, Hoggard J, Chen YH. Claudin-7 Modulates Cl- and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. Int J Mol Sci 2019; 20 (15): 3798–812.
Tummala R, Wolle D, Barwe SP, et al. Expression of Na,K-ATPase-beta(1) subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother Pharmacol 2009; 64 (6): 1187–94.
Kedves AT, Gleim S, Liang X, et al. Recurrent ubiquitin B silencing in gynecological cancers establishes dependence on ubiquitin C. J Clin Invest 2017; 127 (12): 4554–568.