1.Dynamics of T Cell-Mediated Immune Signaling Network During Pathogenesis of Chronic Obstructive Pulmonary Disease
Chae Min LEE ; Andrew Sehoon KIM ; Minki KIM ; Jae Woong JEONG ; Sugyeong JO ; Nahee HWANG ; Sungsoon FANG
Yonsei Medical Journal 2025;66(6):354-365
Purpose:
Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns.
Materials and Methods:
Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions.
Results:
Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management.
Conclusion
The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.
2.Dynamics of T Cell-Mediated Immune Signaling Network During Pathogenesis of Chronic Obstructive Pulmonary Disease
Chae Min LEE ; Andrew Sehoon KIM ; Minki KIM ; Jae Woong JEONG ; Sugyeong JO ; Nahee HWANG ; Sungsoon FANG
Yonsei Medical Journal 2025;66(6):354-365
Purpose:
Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns.
Materials and Methods:
Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions.
Results:
Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management.
Conclusion
The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.
3.Recurrence Dynamics of Pathological N2 Non–Small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor
In Ha KIM ; Geun Dong LEE ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):105-115
Purpose:
This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC).
Materials and Methods:
From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared.
Results:
In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease.
Conclusion
The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.
4.Differences in the Prognostic Impact between Single-Zone and Multi-Zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer
Shia KIM ; Geun Dong LEE ; SeHoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):95-104
Purpose:
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods:
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results:
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.
5.Dynamics of T Cell-Mediated Immune Signaling Network During Pathogenesis of Chronic Obstructive Pulmonary Disease
Chae Min LEE ; Andrew Sehoon KIM ; Minki KIM ; Jae Woong JEONG ; Sugyeong JO ; Nahee HWANG ; Sungsoon FANG
Yonsei Medical Journal 2025;66(6):354-365
Purpose:
Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns.
Materials and Methods:
Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions.
Results:
Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management.
Conclusion
The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.
6.Recurrence Dynamics of Pathological N2 Non–Small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor
In Ha KIM ; Geun Dong LEE ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):105-115
Purpose:
This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC).
Materials and Methods:
From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared.
Results:
In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease.
Conclusion
The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.
7.Differences in the Prognostic Impact between Single-Zone and Multi-Zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer
Shia KIM ; Geun Dong LEE ; SeHoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):95-104
Purpose:
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods:
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results:
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.
8.Dynamics of T Cell-Mediated Immune Signaling Network During Pathogenesis of Chronic Obstructive Pulmonary Disease
Chae Min LEE ; Andrew Sehoon KIM ; Minki KIM ; Jae Woong JEONG ; Sugyeong JO ; Nahee HWANG ; Sungsoon FANG
Yonsei Medical Journal 2025;66(6):354-365
Purpose:
Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns.
Materials and Methods:
Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions.
Results:
Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management.
Conclusion
The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.
9.Recurrence Dynamics of Pathological N2 Non–Small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor
In Ha KIM ; Geun Dong LEE ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):105-115
Purpose:
This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC).
Materials and Methods:
From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared.
Results:
In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease.
Conclusion
The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.
10.Differences in the Prognostic Impact between Single-Zone and Multi-Zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer
Shia KIM ; Geun Dong LEE ; SeHoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Cancer Research and Treatment 2025;57(1):95-104
Purpose:
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods:
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results:
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

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