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The differential analysis of serum HE4 levels in epithelial ovarian cancer and other malignant tumors
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Abstracts / Gynecologic Oncology 145 (2017) 2–220
Fig. 1. Progression-free surviva; (PFSP distribution censored at 60 months from diagnosis for patients with low , mid or high MELK expression level. Distributions compared using log-rank test.
The sensitivity of HE4 as a biomarker for malignancy was calculated for each category with a cutoff of N70.0 pM. Results: A total of 984 patients were included in the meta-analysis. There were 230 premenopausal and 754 postmenopausal patients. When examining all malignancies, HE4 was elevated in 71.7% of the patients. In women with EOC, serum HE4 was elevated in 84.8% (n = 624) of the cases. Analysis of histologic subtypes revealed 90.0% (n = 391) of serous, 84.9% (n = 73) of endometrioid, 45.2% (n = 42) of mucinous, 86.3% (n = 51) of mixed, and 69.4% (n = 36) of clear cell tumors had elevated serum HE4 levels. In addition, serum HE4 was elevated in 60.9%, 84.3%, and 88.6% of grade I (n = 69), II (n = 83), and III (n = 465) EOCs, respectively, and in 65.5% of stage I-II (n = 194) and 93.6% of stage III-IV (n = 424) EOCs, respectively. LMP tumors, germ cell tumors, and cervical cancers were elevated in 39.5% (n = 129), 23.1% (n =13), and 18.2% (n = 11) of patients, respectively. Serum HE4 levels were elevated in only 42.5% (n = 40) of nongynecologic metastatic cancers to the ovary. Conclusion: HE4 is a sensitive marker for EOCs, particularly with advancing stage and grade. HE4 is also a marker for early-stage EOC. HE4 is not often expressed in non-EOC, other gynecologic cancers, or nongynecologic metastatic tumors. This is a positive finding as HE4 will tend to have greater specificity for EOC with a high sensitivity. doi:10.1016/j.ygyno.2017.03.206
179 - Poster Session Variations of gene expression continuously accumulated according to progression of ovarian cancer recurrence W. Yanga, J. Kongb, H.J. Kima, H. Chob, S. Kimc, H. Shinc, E. Leec, D.B. Chaya,, J.H. Kima. aGangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, bGangnam Severance Hospital, Seoul, South Korea, cYonsei University College of Medicine, Seoul, South Korea Fig. 2. Overall survival (OS) distribution censored at 60 months from diagnosis for patients with low , mid or high MELK expression level. Distributions compared using log-rank test.
doi:10.1016/j.ygyno.2017.03.205
178 - Poster Session The differential analysis of serum HE4 levels in epithelial ovarian cancer and other malignant tumors J.E. Mitchella, M.C. Millerb, R. Singhc, G. Messerlianc, R.G. Moorec. a University of Rochester Medical Center, Rochester, NY, USA, bWeill Cornell Medical College, New York, NY, USA, cBrown University, Women and Infants Hospital, Providence, RI, USA Objective: The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, the differential expression of HE4 in various malignancies and histologic subtypes has not been extensively reported. The goal of this study was to determine the differential expression of serum HE4 levels in EOC subtypes and other gynecologic and nongynecologic malignancies. Method: This was an institutional review board-approved trial that examined preoperative serum HE4 levels from patients diagnosed with various malignancies. A database was created by compiling 6 clinical trials. Serum HE4 levels were determined for each histologic group, with EOCs subdivided by histologic subtype, grade, and stage.
Objective: Ovarian cancer has a high incidence of recurrence by spontaneous or adaptive chemoresistance. Thus, the cause of ovarian cancer recurrence is an essential research theme for overcoming ovarian cancer. Primary ovarian cancer tissue, recurrent cancer tissue, and additional recurrent cancer tissue in the same patient were analyzed for gene expression profiling via RNA sequencing, and its effectiveness for clinical application was evaluated. Method: A total of 87 FFPE ovarian cancer tissue blocks in 40 ovarian cancer patients were provided by the Korea Gynecologic Cancer bank (KGCB, http://www.kgcb.or.kr) and Gangnam Severance Hospital. Total RNA were extracted from 5 tissue sections (10-um thickness) using RNeasy FFPE kit (QIAZEN). RNA sequencing using 100 ng of total RNA was performed via Ion AmpliSeq Transcriptome (Thermo Fisher Scientific). The euclidean distances and differentially expressed genes were analyzed using DESeq software in R platform. In this study, approval was obtained from the institutional review board of Gangnam Serverance Hospital. Results: The correlation distance between primary cancer and recurrent cancer were significantly longer in the euclidean distances analysis, but the correlation interval between recurrent cancer and additional recurrent cancer was not a consistent pattern. According to differentially expressed gene analysis, total variation of gene expression is 960 genes between primary cancer and recurrent cancer (2-fold upregulated gene is 557; 2-fold downregulated gene is 403). However, the variation of gene expression is only 196 genes in comparison with recurrent cancer and additional recurrent cancer (2-fold upregulated gene is 126 genes and 2-fold downregulated gene is 70 genes). Therefore, the range of gene expression variation according to progression of recurrence was less than in starting point to cancer, but gene expression variation was sustainedly occurred.
Abstracts / Gynecologic Oncology 145 (2017) 2–220
Fig. 1. Progression-free surviva; (PFSP distribution censored at 60 months from diagnosis for patients with low , mid or high MELK expression level. Distributions compared using log-rank test.
The sensitivity of HE4 as a biomarker for malignancy was calculated for each category with a cutoff of N70.0 pM. Results: A total of 984 patients were included in the meta-analysis. There were 230 premenopausal and 754 postmenopausal patients. When examining all malignancies, HE4 was elevated in 71.7% of the patients. In women with EOC, serum HE4 was elevated in 84.8% (n = 624) of the cases. Analysis of histologic subtypes revealed 90.0% (n = 391) of serous, 84.9% (n = 73) of endometrioid, 45.2% (n = 42) of mucinous, 86.3% (n = 51) of mixed, and 69.4% (n = 36) of clear cell tumors had elevated serum HE4 levels. In addition, serum HE4 was elevated in 60.9%, 84.3%, and 88.6% of grade I (n = 69), II (n = 83), and III (n = 465) EOCs, respectively, and in 65.5% of stage I-II (n = 194) and 93.6% of stage III-IV (n = 424) EOCs, respectively. LMP tumors, germ cell tumors, and cervical cancers were elevated in 39.5% (n = 129), 23.1% (n =13), and 18.2% (n = 11) of patients, respectively. Serum HE4 levels were elevated in only 42.5% (n = 40) of nongynecologic metastatic cancers to the ovary. Conclusion: HE4 is a sensitive marker for EOCs, particularly with advancing stage and grade. HE4 is also a marker for early-stage EOC. HE4 is not often expressed in non-EOC, other gynecologic cancers, or nongynecologic metastatic tumors. This is a positive finding as HE4 will tend to have greater specificity for EOC with a high sensitivity. doi:10.1016/j.ygyno.2017.03.206
179 - Poster Session Variations of gene expression continuously accumulated according to progression of ovarian cancer recurrence W. Yanga, J. Kongb, H.J. Kima, H. Chob, S. Kimc, H. Shinc, E. Leec, D.B. Chaya,, J.H. Kima. aGangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, bGangnam Severance Hospital, Seoul, South Korea, cYonsei University College of Medicine, Seoul, South Korea Fig. 2. Overall survival (OS) distribution censored at 60 months from diagnosis for patients with low , mid or high MELK expression level. Distributions compared using log-rank test.
doi:10.1016/j.ygyno.2017.03.205
178 - Poster Session The differential analysis of serum HE4 levels in epithelial ovarian cancer and other malignant tumors J.E. Mitchella, M.C. Millerb, R. Singhc, G. Messerlianc, R.G. Moorec. a University of Rochester Medical Center, Rochester, NY, USA, bWeill Cornell Medical College, New York, NY, USA, cBrown University, Women and Infants Hospital, Providence, RI, USA Objective: The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, the differential expression of HE4 in various malignancies and histologic subtypes has not been extensively reported. The goal of this study was to determine the differential expression of serum HE4 levels in EOC subtypes and other gynecologic and nongynecologic malignancies. Method: This was an institutional review board-approved trial that examined preoperative serum HE4 levels from patients diagnosed with various malignancies. A database was created by compiling 6 clinical trials. Serum HE4 levels were determined for each histologic group, with EOCs subdivided by histologic subtype, grade, and stage.
Objective: Ovarian cancer has a high incidence of recurrence by spontaneous or adaptive chemoresistance. Thus, the cause of ovarian cancer recurrence is an essential research theme for overcoming ovarian cancer. Primary ovarian cancer tissue, recurrent cancer tissue, and additional recurrent cancer tissue in the same patient were analyzed for gene expression profiling via RNA sequencing, and its effectiveness for clinical application was evaluated. Method: A total of 87 FFPE ovarian cancer tissue blocks in 40 ovarian cancer patients were provided by the Korea Gynecologic Cancer bank (KGCB, http://www.kgcb.or.kr) and Gangnam Severance Hospital. Total RNA were extracted from 5 tissue sections (10-um thickness) using RNeasy FFPE kit (QIAZEN). RNA sequencing using 100 ng of total RNA was performed via Ion AmpliSeq Transcriptome (Thermo Fisher Scientific). The euclidean distances and differentially expressed genes were analyzed using DESeq software in R platform. In this study, approval was obtained from the institutional review board of Gangnam Serverance Hospital. Results: The correlation distance between primary cancer and recurrent cancer were significantly longer in the euclidean distances analysis, but the correlation interval between recurrent cancer and additional recurrent cancer was not a consistent pattern. According to differentially expressed gene analysis, total variation of gene expression is 960 genes between primary cancer and recurrent cancer (2-fold upregulated gene is 557; 2-fold downregulated gene is 403). However, the variation of gene expression is only 196 genes in comparison with recurrent cancer and additional recurrent cancer (2-fold upregulated gene is 126 genes and 2-fold downregulated gene is 70 genes). Therefore, the range of gene expression variation according to progression of recurrence was less than in starting point to cancer, but gene expression variation was sustainedly occurred.