PMID- 25973320 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150514 LR - 20220311 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 5 IP - 2 DP - 2015 TI - Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer. PG - 830-43 AB - BACKGROUND: Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the roles of Lewis y antigen and the markers associated with cell-adhesion-mediated drug resistance (CAM-DR) in patients with EOC. METHODS: 92 EOC patients who were treated with systemic chemotherapy after cytoreductive surgery were included in this analysis. Patients were divided into two groups, chemotherapy sensitive (n = 56) and resistant (n = 36). Immunohistochemical (IHC) staining for Lewis y and CAM-DR-related cell surface proteins including CD44, CD147, HE4 (Human epididymis protein 4), integrin alpha5, beta1, alphav and beta3 were conducted on tissues collected during primary debulking surgery. Using multivariate logistic regressions, IHC results were compared to clinical variables and chemotherapy resistance to determine possible correlations. The relationships between IHC expression and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox regression analysis. RESULTS: Membranous expression of Lewis y and all these CAM-DR-related markers were significantly higher in the resistant group than that of the sensitive group (all P < 0.01). Multivariate regression analysis revealed that high expression of Lewis y, CD44, HE4, integrin alpha5 and beta1 as well as advanced FIGO stage were independent risk factors for chemotherapy resistance (all P < 0.05). Advanced FIGO stage, lymph node metastasis and high expression of Lewis y, CD44, CD147, HE4, integrin alpha5, beta1 were associated with a shorter PFS and OS (all P < 0.05). Moreover, multivariate COX analysis demonstrated that the following variates were independent predictors of worse PFS and OS survival: late FIGO stage (P = 0.013, 0.049), high expressions of Lewis y (P = 0.010, 0.036), HE4 (P = 0.006, 0.013) and integrin beta1 (PFS, P = 0.003), integrin alpha5 (OS, P = 0.019). CONCLUSION: Membranous expression of Lewis y and CAM-DR-related markers including CD44, CD147, HE4, integrin alpha5, beta1, alphav and beta3 are associated with the development of chemotherapy resistance. High expression of Lewis y antigen and CAM-DR-related markers including CD44, CD147, HE4, integrin alpha5 and beta1 are independent markers for PFS and OS, in which Lewis y and HE4 are the most significant. FAU - Zhu, Lian-Cheng AU - Zhu LC AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Gao, Jian AU - Gao J AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Hu, Zhen-Hua AU - Hu ZH AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Schwab, Carlton L AU - Schwab CL AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine 333 Cedar Street, PO Box 208063, New Haven, Connecticut 06520-8063, USA. FAU - Zhuang, Hui-Yu AU - Zhuang HY AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Tan, Ming-Zi AU - Tan MZ AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Yan, Li-Mei AU - Yan LM AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Liu, Juan-Juan AU - Liu JJ AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Zhang, Dan-Ye AU - Zhang DY AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. FAU - Lin, Bei AU - Lin B AD - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University 36 Sanhao Street, Shenyang, Liaoning, 110004, China. LA - eng PT - Journal Article DEP - 20150115 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC4396026 OTO - NOTNLM OT - CAM-DR OT - Epithelial ovarian cancer OT - HE4 OT - Lewis y OT - chemotherapy resistance OT - prognosis EDAT- 2015/05/15 06:00 MHDA- 2015/05/15 06:01 PMCR- 2015/01/15 CRDT- 2015/05/15 06:00 PHST- 2014/11/10 00:00 [received] PHST- 2015/01/15 00:00 [accepted] PHST- 2015/05/15 06:00 [entrez] PHST- 2015/05/15 06:00 [pubmed] PHST- 2015/05/15 06:01 [medline] PHST- 2015/01/15 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2015 Jan 15;5(2):830-43. eCollection 2015.