CD133, CD44, and ALDH1A1 as cancer stem cell markers and prognostic factors in epithelial ovarian cancer
BACKGROUND Ovarian cancer is a heterogeneous disease, and most patients are diagnosed at an advanced stage. Epithelial ovarian cancer type II is characterized by rapid tumor growth and is genetically more labile than type I. This study was aimed to demonstrate the prognostic value of CSC by using the markers CD133, CD44, and ALDH1A1 in EOC.
METHODS Clinicopathological and demographic data were collected from medical records. The markers CD133, CD44, and ALDH1A1 were examined with flow cytometry and immunohistochemistry. Cancer stem cell (CSC) marker expression in patients with ovarian cancer types I and II were related to chemotherapy and survival. In multivariate analysis, the prognosis model was tested for ten months.
RESULTS The largest demographic consisted of patients aged â‰¥45 years, with stage I, poor differentiation, and type II, of which there were 40 samples (72.7%), 23 samples (41.8%), 30 samples (54.5%), and 16 samples (29.1%), respectively. There is a high correlation between the 10-month chemotherapy response and the 4 variables, i.e., age â‰¥45 years, type II, stage IIIâ€“IV, and CD44, with an ROC of 80.75% and a post-test probability of 82.5%. Using the ROC curve, the highest chemoresistance score was 0.841, based on the combination of CSCs markers and clinicopathological factors, that is stage IIIâ€“IV, age â‰¥45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1.
CONCLUSIONS CSC (CD133, CD44, and ALDH1A1) markers and clinicopathological factors are prognostic of epithelial ovarian cancer.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer Statistics, 2008. CA Cancer J Clin. 2008;58(2):71-96. https://doi.org/10.3322/CA.2007.0010
Boyle P, Levin B. World cancer report 2008. France; IARC Press; 2008.
Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34(3):433-43. https://doi.org/10.1097/PAS.0b013e3181cf3d79
Agarwal R, Kaye SB. Prognostic factors in ovarian cancer: how close are we to a complete picture? Ann Oncol. 2005;16(1):4-6. https://doi.org/10.1093/annonc/mdi104
Rizzo S, Hersey JM, Mellor P, Dai W, Santos-Silva A, Liber D, et al. Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther. 2011;10(2):325-35. https://doi.org/10.1158/1535-7163.MCT-10-0788
Rivas-Corchado LM, GonzÃ¡lez-Geroniz M, HernÃ¡ndez-Herrera RJ. Epidemiological profile of ovarian cancer. Ginecol Obstet Mex. 2011;79(9):558-64.
GLOBOCAN. Estimated Incidence, Mortality and prevalence worldwide in 2012. France; 2012.
Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of female reproductive organs. 4th ed. France: International Agency for Research on Cancer (IARC); 2014.
Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative ovarian cancer group. Am J Epidemiol. 1992;136(10):1184-203. https://doi.org/10.1093/oxfordjournals.aje.a116427
SillanpÃ¤Ã¤ S, Anttila MA, Voutilainen K, Tammi RH, Tammi MI, Saarikoski SV, et al. CD44 expression indicates favorable prognosis in epithelial ovarian cancer. Clin Cancer Res. 2003;9(14):5318-24.
Onal Y, Kostek O, Hacioglu MB, Erdogan B, Kodaz H, Bekmez ET, et al. Assessment of prognostic factors in epithelial ovarian cancer. Eurasian J Med Oncol. 2017;1(2):61-8. https://doi.org/10.14744/ejmo.2017.43531
Skirnisdottir I, Seidal T, Ã…kerud H. Differences in clinical and biological features between type I and type II tumors in FIGO stages I-II epithelial ovarian carcinoma. Int J Gynecol Cancer. 2015;25(7):1239-47. https://doi.org/10.1097/IGC.0000000000000484
Senbanjo LT, Chellaiah MA. CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front Cell Dev Biol. 2017;5:18. https://doi.org/10.3389/fcell.2017.00018
Burgos-Ojeda D, Rueda BR, Buckanovich RJ. Ovarian cancer stem cell markers: prognostic and therapeutic implications. Cancer Lett. 2012;322(1):1-7. https://doi.org/10.1016/j.canlet.2012.02.002
Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, et al. Molecular phenotyping of human ovarian cancer stem cells unravel the mechanisms for repair and chemo-resistance. Cell Cycle. 2009;8(1):158-66. https://doi.org/10.4161/cc.8.1.7533
Landen CN Jr, Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, et al. Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 2010;9(12):3186-99. https://doi.org/10.1158/1535-7163.MCT-10-0563
Paik DY, Janzen DM, Schafenacker AM, Velasco VS, Shung MS, Cheng D, et al. Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation. Stem Cells. 2012;30(11):2487-97. https://doi.org/10.1002/stem.1207
Copyright (c) 2019 Nugraha Utama Pelupessy, Andrijono Andrijono, Bambang Sutrisna, Alida R Harahap, Mpu Kanoko, Laila Nuranna, Budiningsih Siregar, Dewi Wulandari
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.