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.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.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.
4.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.
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.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.
7.Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0
Sunho KIM ; Royoung KIM ; Ryeo-Gyeong KIM ; Enjin KO ; Han-Su KIM ; Jihye SHIN ; Daeun CHO ; Yurhee JIN ; Soyeon BAE ; Ye Won JO ; San Ah JEONG ; Yena KIM ; Seoyeon AHN ; Bomi JANG ; Jiheyon SEONG ; Yujin LEE ; Si Eun SEO ; Yujin KIM ; Ha-Jeong KIM ; Hyeji KIM ; Hye-Lynn SUNG ; Hyoyoung LHO ; Jaywon KOO ; Jion CHU ; Juwon LIM ; Youngju KIM ; Kyungyeon LEE ; Yuri LIM ; Meongeun KIM ; Seonjeong HWANG ; Shinhye HAN ; Sohyeun BAE ; Sua KIM ; Suhyeon YOO ; Yeonjeong SEO ; Yerim SHIN ; Yonsoo KIM ; You-Jung KO ; Jihee BAEK ; Hyejin HYUN ; Hyemin CHOI ; Ji-Hye OH ; Da-Young KIM ; Hee-Jo NAM ; Hyun-Seok PARK
Genomics & Informatics 2020;18(3):e33-
This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.
8.Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0
Sunho KIM ; Royoung KIM ; Ryeo-Gyeong KIM ; Enjin KO ; Han-Su KIM ; Jihye SHIN ; Daeun CHO ; Yurhee JIN ; Soyeon BAE ; Ye Won JO ; San Ah JEONG ; Yena KIM ; Seoyeon AHN ; Bomi JANG ; Jiheyon SEONG ; Yujin LEE ; Si Eun SEO ; Yujin KIM ; Ha-Jeong KIM ; Hyeji KIM ; Hye-Lynn SUNG ; Hyoyoung LHO ; Jaywon KOO ; Jion CHU ; Juwon LIM ; Youngju KIM ; Kyungyeon LEE ; Yuri LIM ; Meongeun KIM ; Seonjeong HWANG ; Shinhye HAN ; Sohyeun BAE ; Sua KIM ; Suhyeon YOO ; Yeonjeong SEO ; Yerim SHIN ; Yonsoo KIM ; You-Jung KO ; Jihee BAEK ; Hyejin HYUN ; Hyemin CHOI ; Ji-Hye OH ; Da-Young KIM ; Hee-Jo NAM ; Hyun-Seok PARK
Genomics & Informatics 2020;18(3):e33-
This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.
9.The Effect of Psychological Factors on Postoperative Pain in Gastric Tumor Patients after Endoscopic Submucosal Dissection
Joon Hyub LEE ; Han Ho JEON ; San LEE ; Hyeok LEE ; Seung Taek OH ; Jhin Goo CHANG ; Woo Young IM ; Jaesub PARK ; Won Jung CHOI
Korean Journal of Psychosomatic Medicine 2018;26(1):68-75
OBJECTIVES: Since pain in cancer patients is an important factor that greatly affects the quality of life and prognosis, many attempts have been actively made to reduce the pain. Despite continuous effort on reducing pain after Endoscopic submucosal dissection (ESD), research has not been done on psychological factors as much as on biological factors affecting pain. The objective of this study is to investigate the psychological factors affecting postoperative pain in gastric tumor patients who underwent gastric ESD. METHODS: 91 gastric tumor patients who visited National Health Service Ilsan Hospital in Korean between May 2015 and June 2016, and received ESD were evaluated. Baseline characteristics including sociodemographic factors, anxiety, depression, and resilience were evaluated before the procedure. Multivariate logistic regression was done to analyze factors affecting postoperative pain. RESULTS: The group with high postoperative pain showed lower alcohol consumption and higher depressive symptom scores than the group with low postoperative pain. Also, the group with high postoperative pain showed lower total resilience score with lower subtotal scores in self-control and positive item. Multivariate logistic regression analysis of the postoperative pain showed that patients with lower score in self-control of resilience [odd ratio (OR), 0.911 ; 95% CI, 0.854–0.971, p=0.004) reported more pain after ESD. CONCLUSIONS: This study showed that patients with lower self-control ability of resilience felt more pain after ESD. Among the psychological factors evaluated in this study, resilience of an individual seems to have effect on pain.
Alcohol Drinking
;
Anxiety
;
Biological Factors
;
Depression
;
Humans
;
Logistic Models
;
National Health Programs
;
Pain, Postoperative
;
Prognosis
;
Psychology
;
Quality of Life
;
Self-Control
10.Comparison of the clinical outcome of frozen-thawed embryo transfer with and without pretreatment with a gonadotropin-releasing hormone agonist.
Jieun KANG ; Jisun PARK ; Dawn CHUNG ; San Hui LEE ; Eun Young PARK ; Kyung Hee HAN ; Seoung Jin CHOI ; In Bai CHUNG ; Hyuck Dong HAN ; Yeon Soo JUNG
Obstetrics & Gynecology Science 2018;61(4):489-496
OBJECTIVE: To describe the clinical outcomes of frozen-thawed embryo transfer (FET) with artificial preparation of the endometrium, using a combination of estrogen (E2) and progesterone (P4) with or without a gonadotropin-releasing hormone agonist (GnRHa), and the modified natural cycle (MNC) with human chorionic gonadotropin (hCG) trigger. METHODS: In this retrospective study, we evaluated 187 patients during 3 years (February 2012–April 2015). The patients were allocated to the following treatment groups: group A, comprising 113 patients (181 cycles) who received GnRHa+E2+P4; group B, comprising 49 patients (88 cycles) who received E2+P4; and group C, comprising 25 patients (42 cycles) who received hCG+P4. The inclusion criteria were regular menstrual cycles (length 24–35 days) and age 21–45 years. RESULTS: The primary outcome of the study — implantation rate (IR) per embryo transferred — was not statistically different among the 3 groups. Similar results were found for the IRs with fetal heartbeat per embryo transferred (68/181 [37.6%] in group A vs. 22/88 [25.0%] in group B vs. 14/42 [33.3%] in group C) and for the live birth rates (LBRs) per embryo transferred (56/181 [30.9%] in group A vs. 18/88 [20.5%] in group B vs. 11/42 [26.2%] in group C). CONCLUSION: Although the pregnancy outcomes were better in the hormone therapy with GnRHa group, hormone therapy FET with GnRHa for pituitary suppression did not result in significantly improved IRs and LBRs when compared with hormone therapy FET without GnRHa or MNC FET.
Chorionic Gonadotropin
;
Embryo Transfer*
;
Embryonic Structures*
;
Endometrium
;
Estrogens
;
Female
;
Gonadotropin-Releasing Hormone*
;
Humans
;
Infertility
;
Live Birth
;
Menstrual Cycle
;
Pregnancy
;
Pregnancy Outcome
;
Progesterone
;
Retrospective Studies

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