1.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.
2.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.
3.Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis
Seung-Hoon BAEK ; Seungbae OH ; Bum-Jin SHIM ; Jeong Joon YOO ; Jung-Mo HWANG ; Tae-Young KIM ; Seung-Cheol SHIM
Hip & Pelvis 2024;36(4):234-249
Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.
4.Capsular Contracture After Postmastectomy Radiation in Implant-Based Breast Reconstruction:Effect of Implant Pocket and Two-Stage Surgery
Sohyun MOON ; Kyunghyun MIN ; Tae Ho KIM ; Jung Hwan UM ; Yoonwon KOOK ; Seung Ho BAEK ; In Sik YUN ; Tai Suk ROH ; Soong June BAE ; Joon JEONG ; Sung Gwe AHN ; Young Seok KIM
Journal of Breast Cancer 2024;27(6):395-406
Capsular contracture (CC) is a concerning issue for individuals undergoing postmastectomy radiation therapy (PMRT) with implant-based breast reconstruction. This study investigated whether the extent of CC and implant migration differs based on implant placement and the reconstruction stage. Insertion plane and stage of breast implants were investigated, and the presence and severe cases of CC and implant migration were analyzed. Among 195 participants, 83 were in the pre-pectoral group, and 112 were in the sub-pectoral group. Two-staged surgery was performed on 116 patients, while 79 underwent direct-to-implant (DTI).Notably, The occurrence of CC (prepectoral, 17 [20.48%] and subpectoral, 42 [37.50%];p = 0.011), CC severity (prepectoral, 4 [4.82%] and subpectoral, 17 [15.17%]; p = 0.021), and implant upward migration (prepectoral, 15 [18.07%] and subpectoral, 38 [33.92%]; p = 0.014) significantly varied between the two groups. The incidence of CC was more common in the DTI group (odds ratio [OR], 2.283; 95% confidence interval [CI], 1.164–4.478). Furthermore, subpectoral placement was an independent risk factor for occurrence (OR, 2.989; 95% CI, 1.476–6.054) and severity of CC (OR, 38.552; 95% CI, 1.855–801.186) and upward implant migration (OR, 2.531; 95% CI, 1.263–5.071). Our findings suggest that pre-pectoral reconstruction and the two-stage operation benefit patients who may undergo PMRT. These approaches can help reduce the incidence of CC and abnormal implant migration following radiation, leading to improved aesthetic outcomes and greater patient satisfaction.
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.Capsular Contracture After Postmastectomy Radiation in Implant-Based Breast Reconstruction:Effect of Implant Pocket and Two-Stage Surgery
Sohyun MOON ; Kyunghyun MIN ; Tae Ho KIM ; Jung Hwan UM ; Yoonwon KOOK ; Seung Ho BAEK ; In Sik YUN ; Tai Suk ROH ; Soong June BAE ; Joon JEONG ; Sung Gwe AHN ; Young Seok KIM
Journal of Breast Cancer 2024;27(6):395-406
Capsular contracture (CC) is a concerning issue for individuals undergoing postmastectomy radiation therapy (PMRT) with implant-based breast reconstruction. This study investigated whether the extent of CC and implant migration differs based on implant placement and the reconstruction stage. Insertion plane and stage of breast implants were investigated, and the presence and severe cases of CC and implant migration were analyzed. Among 195 participants, 83 were in the pre-pectoral group, and 112 were in the sub-pectoral group. Two-staged surgery was performed on 116 patients, while 79 underwent direct-to-implant (DTI).Notably, The occurrence of CC (prepectoral, 17 [20.48%] and subpectoral, 42 [37.50%];p = 0.011), CC severity (prepectoral, 4 [4.82%] and subpectoral, 17 [15.17%]; p = 0.021), and implant upward migration (prepectoral, 15 [18.07%] and subpectoral, 38 [33.92%]; p = 0.014) significantly varied between the two groups. The incidence of CC was more common in the DTI group (odds ratio [OR], 2.283; 95% confidence interval [CI], 1.164–4.478). Furthermore, subpectoral placement was an independent risk factor for occurrence (OR, 2.989; 95% CI, 1.476–6.054) and severity of CC (OR, 38.552; 95% CI, 1.855–801.186) and upward implant migration (OR, 2.531; 95% CI, 1.263–5.071). Our findings suggest that pre-pectoral reconstruction and the two-stage operation benefit patients who may undergo PMRT. These approaches can help reduce the incidence of CC and abnormal implant migration following radiation, leading to improved aesthetic outcomes and greater patient satisfaction.
7.Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis
Seung-Hoon BAEK ; Seungbae OH ; Bum-Jin SHIM ; Jeong Joon YOO ; Jung-Mo HWANG ; Tae-Young KIM ; Seung-Cheol SHIM
Hip & Pelvis 2024;36(4):234-249
Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.
8.Capsular Contracture After Postmastectomy Radiation in Implant-Based Breast Reconstruction:Effect of Implant Pocket and Two-Stage Surgery
Sohyun MOON ; Kyunghyun MIN ; Tae Ho KIM ; Jung Hwan UM ; Yoonwon KOOK ; Seung Ho BAEK ; In Sik YUN ; Tai Suk ROH ; Soong June BAE ; Joon JEONG ; Sung Gwe AHN ; Young Seok KIM
Journal of Breast Cancer 2024;27(6):395-406
Capsular contracture (CC) is a concerning issue for individuals undergoing postmastectomy radiation therapy (PMRT) with implant-based breast reconstruction. This study investigated whether the extent of CC and implant migration differs based on implant placement and the reconstruction stage. Insertion plane and stage of breast implants were investigated, and the presence and severe cases of CC and implant migration were analyzed. Among 195 participants, 83 were in the pre-pectoral group, and 112 were in the sub-pectoral group. Two-staged surgery was performed on 116 patients, while 79 underwent direct-to-implant (DTI).Notably, The occurrence of CC (prepectoral, 17 [20.48%] and subpectoral, 42 [37.50%];p = 0.011), CC severity (prepectoral, 4 [4.82%] and subpectoral, 17 [15.17%]; p = 0.021), and implant upward migration (prepectoral, 15 [18.07%] and subpectoral, 38 [33.92%]; p = 0.014) significantly varied between the two groups. The incidence of CC was more common in the DTI group (odds ratio [OR], 2.283; 95% confidence interval [CI], 1.164–4.478). Furthermore, subpectoral placement was an independent risk factor for occurrence (OR, 2.989; 95% CI, 1.476–6.054) and severity of CC (OR, 38.552; 95% CI, 1.855–801.186) and upward implant migration (OR, 2.531; 95% CI, 1.263–5.071). Our findings suggest that pre-pectoral reconstruction and the two-stage operation benefit patients who may undergo PMRT. These approaches can help reduce the incidence of CC and abnormal implant migration following radiation, leading to improved aesthetic outcomes and greater patient satisfaction.
9.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.
10.Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Su Hwan KANG ; Bon Seok KOO ; Sun Wook KIM ; Dong Gyu NA ; Seung-Kuk BAEK ; So Won OH ; Min Kyoung LEE ; Sang-Woo LEE ; Young Ah LEE ; Yong Sang LEE ; Ji Ye LEE ; Dong-Jun LIM ; Leehi JOO ; Yuh-Seog JUNG ; Chan Kwon JUNG ; Yoon Young CHO ; Yun Jae CHUNG ; Won Bae KIM ; Ka Hee YI ; Ho-Cheol KANG ; Do Joon PARK
International Journal of Thyroidology 2024;17(1):208-244
Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.

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