1.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
2.Robotic Single-Site Plus One-Port Myomectomy versus Robotic Single-Site Plus Two-Port Myomectomy: A Propensity Score Matching Analysis
Su Hyeon CHOI ; Seyeon WON ; Nara LEE ; So Hyun SHIM ; Mi Kyoung KIM ; Mi-La KIM ; Yong Wook JUNG ; Bo Seong YUN ; Hye Sun JUN ; Seok Ju SEONG
Yonsei Medical Journal 2024;65(7):406-412
Purpose:
Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes.
Materials and Methods:
The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups’ surgical outcomes were compared using propensity score matching (PSM) analysis.
Results:
In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients’ baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group.
Conclusion
Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.
3.Exploring the Expression and Function of T Cell Surface Markers Identified through Cellular Indexing of Transcriptomes and Epitopes by Sequencing
Joon Yeon HWANG ; Youngtaek KIM ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(9):544-555
Purpose:
By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems.
Materials and Methods:
This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data.The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed.
Results:
We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8+ T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset.
Conclusion
In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease.
4.Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study
Jie-Hyun KIM ; Hwoon-Yong JUNG ; In Kyung YOO ; Seon-Young PARK ; Jae Gyu KIM ; Jae Kyu SUNG ; Jin Seok JANG ; Gab Jin CHEON ; Kyoung Oh KIM ; Tae Oh KIM ; Soo Teik LEE ; Kwang Bum CHO ; Hoon Jai CHUN ; Jong-Jae PARK ; Moo In PARK ; Jae-Young JANG ; Seong Woo JEON ; Jin Woong CHO ; Dae Hwan KANG ; Gwang Ha KIM ; Jae J. KIM ; Sang Gyun KIM ; Nayoung KIM ; Yong Chan LEE ; Su Jin HONG ; Hyun-Soo KIM ; Sora LEE ; Sang Woo LEE
Gut and Liver 2024;18(1):70-76
Background/Aims:
H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis.
Methods:
A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared.
Results:
According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different.
Conclusions
DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).
5.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
6.Epidemiological and Clinical Characteristics of Women Living with HIV in Korea
Sang Min AHN ; Yong Seop LEE ; Min HAN ; Jung Ah LEE ; Jae Eun SEONG ; Yae Jee BAEK ; JongHoon HYUN ; Jung Ho KIM ; Jin Young AHN ; Dong Hyun OH ; Su Jin JEONG ; Ji Hyeon BAEK ; Nam Su KU ; Hee Kyoung CHOI ; Yoonseon PARK ; BumSik CHIN ; Young Keun KIM ; Joon Sup YEOM ; Young Hwa CHOI ; Jun Yong CHOI
Infection and Chemotherapy 2024;56(3):369-377
Background:
While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea.
Materials and Methods:
We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023.
Results:
A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively.
Conclusion
This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.
7.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
8.Association between Metabolic Factors and Gastric Cancer
Su Youn NAM ; Oh Kyoung KWON ; Seong Woo JEON
Journal of Digestive Cancer Research 2024;12(3):216-223
Background/Aims:
We investigated sex- and stage-specific associations of body mass index (BMI), fasting glucose, and high-density lipoprotein cholesterol (HDL-C) with gastric cancer.
Methods:
In total, 3,382 patients with gastric cancer and 19,609 healthy controls were enrolled. BMI was categorized into five groups. HDL-C was classified as low (< 40 and < 50 mg/ dl in males and females, respectively) and normal (≥ 40 and ≥ 50 mg/dl in males and females, respectively). Logistic regression analysis was performed to calculate odd ratios (ORs) and 95% confidence intervals (CIs).
Results:
After adjustment, low BMI (OR, 1.44; 95% CI, 1.13–1.84), low HDL levels (OR, 2.28;95% CI, 2.07–2.50), and high fasting glucose levels (OR, 2.94; 95% CI, 2.22–2.99) were associated with gastric cancer, whereas high BMI (OR, 0.61–0.81) was inversely associated with gastric cancer. In sex-specific analysis, BMI was inversely associated with gastric cancer only in males (trend: p < 0.001). Low serum HDL and high fasting glucose levels were strongly associated with gastric cancer in both males and females. The effect of high glucose content was more pronounced in females (OR, 4.02) than in males (OR, 2.58). BMI was inversely associated with both AGC (trend: p < 0.001) and EGC (trend: p = 0.001). Low serum HDL and high fasting glucose levels were strongly associated with gastric cancer in EGC and AGC.
Conclusions
The effect of BMI on gastric cancer varies by sex and stage, whereas low HDL levels are associated with gastric cancer regardless of these factors.
9.Epidemiological and Clinical Characteristics of Women Living with HIV in Korea
Sang Min AHN ; Yong Seop LEE ; Min HAN ; Jung Ah LEE ; Jae Eun SEONG ; Yae Jee BAEK ; JongHoon HYUN ; Jung Ho KIM ; Jin Young AHN ; Dong Hyun OH ; Su Jin JEONG ; Ji Hyeon BAEK ; Nam Su KU ; Hee Kyoung CHOI ; Yoonseon PARK ; BumSik CHIN ; Young Keun KIM ; Joon Sup YEOM ; Young Hwa CHOI ; Jun Yong CHOI
Infection and Chemotherapy 2024;56(3):369-377
Background:
While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea.
Materials and Methods:
We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023.
Results:
A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively.
Conclusion
This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.
10.Association between Metabolic Factors and Gastric Cancer
Su Youn NAM ; Oh Kyoung KWON ; Seong Woo JEON
Journal of Digestive Cancer Research 2024;12(3):216-223
Background/Aims:
We investigated sex- and stage-specific associations of body mass index (BMI), fasting glucose, and high-density lipoprotein cholesterol (HDL-C) with gastric cancer.
Methods:
In total, 3,382 patients with gastric cancer and 19,609 healthy controls were enrolled. BMI was categorized into five groups. HDL-C was classified as low (< 40 and < 50 mg/ dl in males and females, respectively) and normal (≥ 40 and ≥ 50 mg/dl in males and females, respectively). Logistic regression analysis was performed to calculate odd ratios (ORs) and 95% confidence intervals (CIs).
Results:
After adjustment, low BMI (OR, 1.44; 95% CI, 1.13–1.84), low HDL levels (OR, 2.28;95% CI, 2.07–2.50), and high fasting glucose levels (OR, 2.94; 95% CI, 2.22–2.99) were associated with gastric cancer, whereas high BMI (OR, 0.61–0.81) was inversely associated with gastric cancer. In sex-specific analysis, BMI was inversely associated with gastric cancer only in males (trend: p < 0.001). Low serum HDL and high fasting glucose levels were strongly associated with gastric cancer in both males and females. The effect of high glucose content was more pronounced in females (OR, 4.02) than in males (OR, 2.58). BMI was inversely associated with both AGC (trend: p < 0.001) and EGC (trend: p = 0.001). Low serum HDL and high fasting glucose levels were strongly associated with gastric cancer in EGC and AGC.
Conclusions
The effect of BMI on gastric cancer varies by sex and stage, whereas low HDL levels are associated with gastric cancer regardless of these factors.

Result Analysis
Print
Save
E-mail