1.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
2.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
3.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
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.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.
6.Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ; Research Committee of the Korean Liver Cancer Association
Gut and Liver 2024;18(5):789-802
Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements.Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.
7.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
8.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.
9.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
10.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.

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