Proteomic discovery of tissue- and serum-based prognostic biomarkers for high-grade serous ovarian carcinoma

( Aeran Seol ),( Se Ik Kim ),( Maria Lee ),( Hee Seung Kim ),( Hyun Hoon Chung ),( Jae-weon Kim ),( Noh Hyun Park ),( Yong-sang Song ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-

Objective: This study aimed to investigate tissue- and serum-based prognostic biomarkers of high-grade serous ovarian carcinoma (HGSOC) through proteomic analysis. Methods: We conducted label-free liquid chromatography-mass spectrometry using chemotherapy-nave, fresh-frozen primary HGSOC specimens(n=12) and compared results between a favorable prognosis group(PFS ≥18 months) and a poor prognosis group (PFS <18 months). We also conducted proteomic profiling of serum samples obtained from chemotherapy-nave, HGSOC patients(n=20). Differentially expressed serum proteins between two groups were compared. Candidate protein biomarkers were validated via immunohistochemistry(IHC) and ELISA using an independent set of chemotherapy-nave primary HGSOC specimens (n=107) and serum samples (n=100), respectively. Results: Among 658 differentially expressed proteins, 288 proteins were upregulated in favorable prognosis group and 370 proteins were upregulated in other group. Using hierarchical clustering, we selected AAT, NFKB, PMVK, VAP1, FABP4, PF4, APOA1, and AGP for further validation via IHC. Survival analyses revealed that high expression of AAT, NFKB, and PMVK were independent biomarkers for favorable PFS. High expression of VAP1, FABP4, and PF4 were identified as independent biomarkers for poor PFS. We constructed models predicting 18-month PFS by combining clinical variables and IHC results. The optimal model was based on initial serum CA-125, germline BRCA1/2 mutations, residual tumors after surgery, FIGO stage, and expression levels of the six proteins. Among six biomarkers, AAT and FABP4 were quantified in serum samples by ELISA. Dose-dependent prognostic significance of each proteins concentration for PFS was observed. A model consisting of serum AAT and FABP4 concentrations and clinical variables showed good performance in predicting poor prognosis groups. Conclusion: The present results elucidate the proteomic landscape of HGSOC and tissue- and serum-based protein biomarkers to predict the prognosis of HGSOC.

Effect of luteal phase support with vaginal progesterone on pregnancy outcomes in natural frozen embryo transfer cycles: A meta-analysis

Seol, Aeran,Shim, Yoo Jin,Kim, Sung Woo,Kim, Seul Ki,Lee, Jung Ryeol,Jee, Byung Chul,Suh, Chang Suk,Kim, Seok Hyun The Korean Society for Reproductive Medicine 2020 Clinical and Experimental Reproductive Medicine Vol.47 No.2

Objective: The purpose of this study was to determine the effect of vaginal progesterone for luteal phase support (LPS) on the clinical pregnancy rate (CPR) in natural frozen embryo transfer (FET) cycles via a meta-analysis. Methods: We performed a meta-analysis of randomized controlled trials (RCTs) and retrospective studies that met our selection criteria. Four online databases (PubMed, Embase, Medline, and the Cochrane Library) were searched between January 2017 and May 2017. Studies were selected according to predefined inclusion criteria and meta-analyzed using R software version 2.14.2. The main outcome measure was CPR. Results: A total of 18 studies were reviewed and assessed for eligibility. One RCT (n = 435) and three retrospective studies (n = 3,033) met the selection criteria. In a meta-analysis of the selected studies, we found no significant difference in the CPR (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.60-1.55) between the vaginal progesterone and control groups. An analysis of the two retrospective cohort studies that reported the live birth rate (LBR) following FET showed a significantly higher LBR in the vaginal progesterone group (OR, 1.72; 95% CI, 1.21-2.46). A subgroup meta-analysis of FET conducted 5 days after injection of human chorionic gonadotropin showed no significant differences between the two groups with regard to the CPR (OR, 1.18; 95% CI, 0.90-1.55) or miscarriage rate (OR, 0.73; 95% CI, 0.36-1.47). Conclusion: The results of this meta-analysis of the currently available literature suggest that LPS with vaginal progesterone in natural FET cycles does not improve the CPR.

Comparative analysis between primary ovarian cancer tissue and metastatic tumor tissue in a advanced high-grade serous ovarian cancer patient

( Aeran Seol ),( Seon Mi Lee ),( Hyun Woong Cho ),( Kyung Jin Min ),( Sanghoon Lee ),( Jin Hwa Hong ),( Jae Yun Song ),( Jae Kwan Lee ),( Nak Woo Lee ) 대한산부인과학회 2023 대한산부인과학회 학술대회 Vol.109 No.-

Development of Tissue Equivalent Materials for a Multi-modality (CT&MRI) Phantom in MRI-guided Radiation Treatment

Yunji Seol,Jina Kim,Aeran Kim,Jinho Hwang,Taegeon Oh,Jin-sol Shin,Hong Seok Jang,Byung Ock Choi,Young-nam Kang 한국물리학회 2018 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.73 No.7

This study proposed to develop a phantom material that can represent the various contrasts of both MRI and CT images and is available to use in MRI-guided radiation treatment. Materials used for making a phantom that can be used for both MRI and CT image were agarose (T2 modifier), gadolinium-based contrast agent (T1 modifier), sodium uoride (CT number modifier), and distilled water. They were mixed at various composition ratios and stirred until transparent. For the relationship between the ingredients and values, 48 samples were manufactured at various composition ratios. The relationship was expressed as equations, to be able to get the composition ratios of organs that we wanted to make. MR relaxation times were measured using 1.5 T MRI equipment. CT scans were performed at 120 kVp and extracted CT numbers from images. Based on the fitted equations derived from the relationship between ingredients and values, materials were manufactured using the composition ratio of human organs; brain (white and gray matter), liver, spleen, kidney, and prostate. The all values were within the reference range, but some exceeded the range due to the image noise. A phantom composed of substitutes made from the derived equations added other substances of different density like bone or lung can be used as an inhomogeneity dose calculation phantom for both CT and MRI. Furthermore, it can be applied to MRI-only based RTP systems and MRI-guided radiation treatment QA in the future.

Development of an Algorithm for Predicting the Thermal Distribution by using CT Image and the Specific Absorption Rate

Jinho Hwang,Aeran Kim,Jina Kim,Yunji Seol,Taegeon Oh,Jin-sol Shin,Hong Seok Jang,Yeon-Sil Kim,Byung Ock Choi,Young-nam Kang 한국물리학회 2018 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.73 No.10

During hyperthermia therapy, cancer cells are heated to a temperature in the range of 40 45 C for a defined time period to damage these cells while keeping healthy tissues at safe temperatures. Prior to hyperthermia therapy, the amount of heat energy transferred to the cancer cells must be predicted. Among various non-invasive methods, the thermal prediction method using the specific absorption rate (SAR) is the most widely used method. The existing methods predict the thermal distribution by using a single constant for the mass density in one organ through assignment. However, because the SAR and the bio heat equation (BHE) vary with the mass density, the mass density of each organ must be accurately considered. In this study, the mass density distribution was calculated using the relationship between the Hounsfield unit and the mass density of tissues in preceding research. The SAR distribution was found using a quasi-static approximation to Maxwell's equation and was used to calculate the potential distribution and the energy distributions for capacitive RF heating. The thermal distribution during exposure to RF waves was determined by solving the BHE with consideration given to the considering contributions of heat conduction and external heating. Compared with reference data for the mass density, our results was within 1%. When the reconstructed temperature distribution was compared to the measured temperature distribution, the difference was within 3%. In this study, the density distribution and the thermal distribution were reconstructed for the agar phantom. Based on these data, we developed an algorithm that could be applied to patients.

Genomic and transcriptomic analysis of high-grade serous ovarian carcinoma

( Se Ik Kim ),( Aeran Seol ),( Maria Lee ),( Hee Seung Kim ),( Hyun Hoon Chung ),( Jae-weon Kim ),( Noh Hyun Park ),( Yong-sang Song ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Objective: High-grade serous ovarian carcinoma (HGSOC) is one of the deadliest female malignancies with worse survival outcome. We aimed to broaden genomic understanding of HGOC, and to aid the development of targeted therapies and prognostic markers for HGOC via next generation sequencing technology. Methods: We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were collected from women diagnosed with HGSOC between 2013 and 2016. In total, 20 patients were enrolled. To enable comprehensive profiling, we performed whole exome sequencing and whole transcriptome sequencing on fresh frozen cancers via the technique of next generation sequencing. Results: We discovered that HGOC is characterized by MUC4 mutations (85%) and TP53 mutations (50%) in almost all tumors. Despite their low prevalence, repeatedly altered genes observed in HGSOC were ERG, ATR, NOTCH4, CSMD3 and KEAP1. We also identified somatic copy number gain on the region of BCL6, PIK3CA, TP63, SOX2 and MYC, and somatic copy number loss on the region of APC, CHEK1 and ATM. To discover candidates for prognostic biomarkers, we conducted differential gene expression analyses. In the poorer survival group, we found increased expression of HOXA9 and HOXA10, the members of homeobox (HOX) gene family, and increased expression of FGFBP1, PDGFRB, F3, BCL2L1 and MAP2K5, which were known to be associated with cell proliferation and survival pathway. In addition, through the analyses of differential splicing, alternative splicing of EME1 was identified as a poor prognostic marker for HGSOC. Conclusion: We successfully obtained genomic and transcriptomic landscape of 20 patients with HGSOC, and discovered therapeutic target genes, as well as prognostic biomarkers.

Comparison of Surgical outcomes between Single-Port Laparoscopic Surgery and da Vinci Single-Port Robotic Surgery

( Jeong-min Kim ),( Aeran Seol ),( Seon-mi Lee ),( Ki-jin Ryu ),( Sanghoon Lee ),( Hyun-tae Park ),( Hyun-woong Cho ),( Kyung-jin Min ),( Jin-hwa Hong ),( Jae-yun Song ),( Jae-kwan Lee ),( Nak-woo Lee 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: The objective of this study is to compare the outcome between SPLS (Single-Port Laparoscopic Surgery) and SPRS (Single-Port Robotic Surgery). Methods: We conducted a retrospective analysis on patients who underwent hysterectomy, ovarian cystectomy, or myomectomy with SPLS or SPRS from January 2020 to July 2022. The primary outcome was operation time, and the secondary outcome was intra-operative complication, post-operative complication, conversion to laparotomy, post-operative Hb change, and hospitalization period. Statistical analysis was performed using SPSS chi-square test and student’s T-test. Results: A total of 566 surgeries included SPLH (Single-port Laparoscopic hysterectomy) (n=148), SPRH (Single-port Robotic hysterectomy) (n=35), SPLC (Single-port Laparoscopic ovarian cystectomy) (n=207), SPRC (Single-port Robotic ovarian cystectomy) (n=108), SPLM (Single-port Laparoscopic myomectomy) (n=12), and SPRM (Single-port Robotic myomectomy) (n=56). Although it was not statistically significant, SPRH, SPRC, SPRM were shorter in operation time than the SPLS groups. None of the case underwent conversion to laparotomy. Incisional hernia occurred as post-operative complications in two patients in the SPLH group, and there was no post-operative complication in the remaining SPRH, SPLC, SPRC, SPLM, and SPRM groups. The post-operative Hb changes were lower in SPRC and SPRM than in SPLC and SPLM, respectively (SPRC vs SPLC, p=0.023; SPRM vs SPLM, p=0.010). The average hospitalization period for SP hysterectomy was 4.55 ± 1.21 days, SP ovarian cystectomy was 4.43 ± 1.34 days, and SP myomectomy was 4.68 ± 1.50 days. Conclusion: SPRS was performed successfully compared to SPLS in hysterectomy, ovarian cystectomy and myomectomy without complications. Therefore, SPRS is feasible and relatively safe for gynecological patients eligible for SP surgery.

생식내분비학

김슬기 ( Yoo Jin Shim ),( Aeran Seol ),( Dayong Lee ),( Seul Ki Kim ),( Jung Ryeol Lee ),( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2019 대한산부인과학회 학술대회 Vol.105 No.-

Objective: To investigate the patterns of estradiol-oocyte ratio (EOR) and estradiol-mature oocyte ratio (EMOR) in patients with breast cancer undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins for fertility preservation. Methods: This retrospective study included 32 breast cancer patients underwent COS for fertility preservation and no patients had previously undergone gonadotoxic treatments. Basal characteristics and in vitro fertilization (IVF) outcomes were compared according to the age of women (age <35 vs. age ≥35) and the starting phase of ovarian stimulation (early follicular phase vs. late follicular phase vs. luteal phase). Results: Patients who were administered with a letrozole-combined regimen, the peak serum estradiol (E2) was maintained at a low level (386.3±346.9 pg/mL). EOR was 52.4±78.8 pg/mL, and EMOR was 71.0±41.2 pg/mL. When the 2 groups were compared according to the age of women (age <35 vs. age ≥35), EOR was 34.5 (22.2-46.5) pg/mL and 40.7 (19.3-65.3) pg/mL, respectively; EMOR was 79.8 (40.8-90.6) pg/mL and 68.8 (44.5-85.9) pg/mL, respectively. There was no significant difference in the IVF outcomes. When the 2 groups were compared according to the starting phase of ovarian stimulation, there were no significant differences in IVF outcomes, EOR and EMOR among the groups. Conclusion: Measuring the peak E2 concentration in breast cancer patients undergoing IVF for fertility preservation with a co-treatment of letrozole allows for the prediction of the numbers of oocytes and mature oocytes.

The serum estradiol/oocyte ratio in patients with breast cancer undergoing ovarian stimulation with letrozole and gonadotropins

( Yoo Jin Shim ),( Aeran Seol ),( Dayong Lee ),( Seul Ki Kim ),( Jung Ryeol Lee ),( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2018 Obstetrics & Gynecology Science Vol.61 No.2

Objective To investigate the patterns of estradiol-oocyte ratio (EOR) and estradiol-mature oocyte ratio (EMOR) in patients with breast cancer undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins for fertility preservation. Methods This retrospective study included 32 breast cancer patients underwent COS for fertility preservation and no patients had previously undergone gonadotoxic treatments. Basal characteristics and in vitro fertilization (IVF) outcomes were compared according to the age of women (age <35 vs. age ≥35) and the starting phase of ovarian stimulation (early follicular phase vs. late follicular phase vs. luteal phase). Results Patients who were administered with a letrozole-combined regimen, the peak serum estradiol (E2) was maintained at a low level (386.3±346.9 pg/mL). EOR was 52.4±78.8 pg/mL, and EMOR was 71.0±41.2 pg/mL. When the 2 groups were compared according to the age of women (age <35 vs. age ≥35), EOR was 34.5 (22.2-46.5) pg/mL and 40.7 (19.3-65.3) pg/mL, respectively; EMOR was 79.8 (40.8-90.6) pg/mL and 68.8 (44.5-85.9) pg/mL, respectively. There was no significant difference in the IVF outcomes. When the 2 groups were compared according to the starting phase of ovarian stimulation, there were no significant differences in IVF outcomes, EOR and EMOR among the groups. Conclusion Measuring the peak E2 concentration in breast cancer patients undergoing IVF for fertility preservation with a co-treatment of letrozole allows for the prediction of the numbers of oocytes and mature oocytes.

Korea Citation Index and Its Macro Bibliometrics

Kim, Sohyeong,Choi, Taejin,Yoon, Aeran,Seol, Sung-Soo Asian Society for Innovation and Policy 2013 Asian Journal of Innovation and Policy Vol.2 No.2

This paper introduces the Korea Citation Index (KCI) and also some macro statistics of KCI. KCI started service since 2008 by the National Research Foundation of Korea (NRF), but the data has been gathered from 1998. Our findings are as follows: heavy reliance on books in humanities, but papers as the main reference in all other disciplines. Impact factor is an increasing trend in all disciplines. Social science has the highest impact factor among all fields. In some fields even in science and engineering areas, there are more KCI papers than Korean JCR papers and impact factors of the KCI are higher than JCR. As for the distinction between nationally and internationally fields or journals, some disciplines in social science are clearly nationally oriented. NSE journals listed in both KCI and JCR, however, are not clear in terms of impact factor, but clear in terms of the numbers of papers.