Investigator

Maria Lee

Seoul National University

MLMaria Lee
Papers(12)
Proteomic landscaping…The new 2023 FIGO sta…Clinical practice gui…Comparison of surviva…Risk Factors Associat…Disparities between U…Proteomic Discovery o…Association between p…Uptake Rate of Risk-R…Comparisons of surviv…Classification of Hig…Comparison of the Pro…
Collaborators(10)
Min Chul ChoiSe Ik KimSeung-Hyuk ShimSo Jin ShinJae-Weon KimJae Yun SongChel Hun ChoiWhan ShinJi Jeong ParkGun Oh Chong
Institutions(10)
Seoul National Univer…University Of UlsanKonkuk University Hos…Keimyung University S…Seoul National Univer…Korea University Anam…Samsung Medical CenterDankook University Ho…National Evidenc Base…Kyungpook National Un…

Papers

Comparison of survival and complications between minimally invasive and open staging surgeries in non-endometrioid endometrial cancer

This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer. Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017). In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004). Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context.

Proteomic Discovery of Plasma Protein Biomarkers and Development of Models Predicting Prognosis of High-Grade Serous Ovarian Carcinoma

Ovarian cancer is one of the most lethal female cancers. For accurate prognosis prediction, this study aimed to investigate novel, blood-based prognostic biomarkers for high-grade serous ovarian carcinoma (HGSOC) using mass spectrometry-based proteomics methods. We conducted label-free liquid chromatography-tandem mass spectrometry using frozen plasma samples obtained from patients with newly diagnosed HGSOC (n = 20). Based on progression-free survival (PFS), the samples were divided into two groups: good (PFS ≥18 months) and poor prognosis groups (PFS <18 months). Proteomic profiles were compared between the two groups. Referring to proteomics data that we previously obtained using frozen cancer tissues from chemotherapy-naïve patients with HGSOC, overlapping protein biomarkers were selected as candidate biomarkers. Biomarkers were validated using an independent set of HGSOC plasma samples (n = 202) via enzyme-linked immunosorbent assay (ELISA). To construct models predicting the 18-month PFS rate, we performed stepwise selection based on the area under the receiver operating characteristic curve (AUC) with 5-fold cross-validation. Analysis of differentially expressed proteins in plasma samples revealed that 35 and 61 proteins were upregulated in the good and poor prognosis groups, respectively. Through hierarchical clustering and bioinformatic analyses, GSN, VCAN, SND1, SIGLEC14, CD163, and PRMT1 were selected as candidate biomarkers and were subjected to ELISA. In multivariate analysis, plasma GSN was identified as an independent poor prognostic biomarker for PFS (adjusted hazard ratio, 1.556; 95% confidence interval, 1.073-2.256; p = 0.020). By combining clinical factors and ELISA results, we constructed several models to predict the 18-month PFS rate. A model consisting of four predictors (FIGO stage, residual tumor after surgery, and plasma levels of GSN and VCAN) showed the best predictive performance (mean validated AUC, 0.779). The newly developed model was converted to a nomogram for clinical use. Our study results provided insights into protein biomarkers, which might offer clues for developing therapeutic targets.

Classification of High-Grade Serous Ovarian Carcinoma by Epithelial-to-Mesenchymal Transition Signature and Homologous Recombination Repair Genes

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of multi-omics data. We used fresh-frozen, chemotherapy-naïve primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next-generation whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutations and others with wild-type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive somatic mutation patterns, yet the implementation of high-dimensional analysis of RNA-seq and application of epithelial-to-mesenchymal (EMT) index onto the HGSOC samples revealed that they can be divided into two subtypes; homologous recombination repair (HRR)-activated type and mesenchymal type. Patients with mesenchymal HGSOC, characterized by the activation of the EMT transcriptional program, low genomic alteration and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (p = 0.002). In validation with The Cancer Genome Atlas (TCGA) HGSOC data, patients with a high EMT index (≥the median) showed significantly worse overall survival than did those with a low EMT index (&lt;the median) (p = 0.030). In conclusion, through a comprehensive multi-omics approach towards our HGSOC cohorts, two distinctive types of HGSOC (HRR-activated and mesenchymal) were identified. Our novel EMT index seems to be a potential prognostic biomarker for HGSOC.

Discrepancy between Cytology and Histology in Cervical Cancer Screening: a Multicenter Retrospective Study (KGOG 1040)

Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells. Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. In our study, 3,798 eligible patients were included. Mean age of patients was 42.7 (19-88) years and mean BMI was 22.5 (16.9-34.1) kg/m². The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475-3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367-0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385-2.469). Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia

AbstractAimThe aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea.MethodsEligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher.ResultsA total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9–44.1) in patients positive for HPV 16/18.The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p &lt; 0.05) compared to Cobas 4800, in aspect of high‐risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p &lt; 0.05).ConclusionThe performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost‐effectiveness of the various commercially available domestic HPV assays.

15Papers
57Collaborators