The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features
Abstract Lung adenocarcinoma (LADC) exhibits high spatial heterogeneity, with distinct spatial variations in pathological features. The distribution of tertiary lymphoid structures (TLS) in LADC is uneven, and different TLS characteristics play unique roles. To investigate the correlation between TL...
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BMC
2025-03-01
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| Series: | World Journal of Surgical Oncology |
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| Online Access: | https://doi.org/10.1186/s12957-025-03751-z |
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| author | Yun Ding Mengting Yu Mengli Xue Wenkang Zong Yangyun Huang Jie Ren Tianxing Guo Daqiang Sun Xiaojie Pan |
| author_facet | Yun Ding Mengting Yu Mengli Xue Wenkang Zong Yangyun Huang Jie Ren Tianxing Guo Daqiang Sun Xiaojie Pan |
| author_sort | Yun Ding |
| collection | DOAJ |
| description | Abstract Lung adenocarcinoma (LADC) exhibits high spatial heterogeneity, with distinct spatial variations in pathological features. The distribution of tertiary lymphoid structures (TLS) in LADC is uneven, and different TLS characteristics play unique roles. To investigate the correlation between TLS features and other pathological characteristics, particularly tumor spread through air spaces (STAS), we analyzed TLS and other pathological features on whole-slide images stained with HE and CD20/CD23. Additionally, the 14-Gene assay was used to assess prognostic risk. Among 388 enrolled LADC patients, 226 (58.2%) were TLS-positive. TLS showed a negative correlation with various adverse pathological features, with boundary-area TLS demonstrating the strongest correlation with STAS quantity (r= -0.324, P < 0.001). Multivariate Cox analysis identified boundary-area TLS as an independent prognostic factor for recurrence-free survival (HR = 0.856, 95% CI = 0.759–0.966, P = 0.026), while mature TLS was an independent factor for overall survival (HR = 0.841, 95% CI = 0.717–0.988, P = 0.035). High-density TLS at the tumor boundary was associated with low-risk stratification by the 14-Gene assay (P = 0.013). This study highlights the negative correlation between TLS and STAS, especially in boundary areas, and emphasizes the impact of tumor microenvironment spatial characteristics on clinical outcomes. Assessment of spatial heterogeneity in LADC facilitates precise risk stratification for patients. |
| format | Article |
| id | doaj-art-a4866cfcffec45faac15345cd12f9390 |
| institution | DOAJ |
| issn | 1477-7819 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj-art-a4866cfcffec45faac15345cd12f93902025-08-20T02:41:32ZengBMCWorld Journal of Surgical Oncology1477-78192025-03-012311910.1186/s12957-025-03751-zThe correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial featuresYun Ding0Mengting Yu1Mengli Xue2Wenkang Zong3Yangyun Huang4Jie Ren5Tianxing Guo6Daqiang Sun7Xiaojie Pan8Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalShengli Clinical Medical College of Fuzhou University Affiliated Provincial HospitalClinical School of Thoracic, Tianjin Medical UniversityClinical School of Thoracic, Tianjin Medical UniversityDepartment of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalClinical School of Thoracic, Tianjin Medical UniversityDepartment of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalClinical School of Thoracic, Tianjin Medical UniversityDepartment of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalAbstract Lung adenocarcinoma (LADC) exhibits high spatial heterogeneity, with distinct spatial variations in pathological features. The distribution of tertiary lymphoid structures (TLS) in LADC is uneven, and different TLS characteristics play unique roles. To investigate the correlation between TLS features and other pathological characteristics, particularly tumor spread through air spaces (STAS), we analyzed TLS and other pathological features on whole-slide images stained with HE and CD20/CD23. Additionally, the 14-Gene assay was used to assess prognostic risk. Among 388 enrolled LADC patients, 226 (58.2%) were TLS-positive. TLS showed a negative correlation with various adverse pathological features, with boundary-area TLS demonstrating the strongest correlation with STAS quantity (r= -0.324, P < 0.001). Multivariate Cox analysis identified boundary-area TLS as an independent prognostic factor for recurrence-free survival (HR = 0.856, 95% CI = 0.759–0.966, P = 0.026), while mature TLS was an independent factor for overall survival (HR = 0.841, 95% CI = 0.717–0.988, P = 0.035). High-density TLS at the tumor boundary was associated with low-risk stratification by the 14-Gene assay (P = 0.013). This study highlights the negative correlation between TLS and STAS, especially in boundary areas, and emphasizes the impact of tumor microenvironment spatial characteristics on clinical outcomes. Assessment of spatial heterogeneity in LADC facilitates precise risk stratification for patients.https://doi.org/10.1186/s12957-025-03751-zTertiary lymphoid structuresTumor spread through air spacesSpatial characteristicsLung adenocarcinoma |
| spellingShingle | Yun Ding Mengting Yu Mengli Xue Wenkang Zong Yangyun Huang Jie Ren Tianxing Guo Daqiang Sun Xiaojie Pan The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features World Journal of Surgical Oncology Tertiary lymphoid structures Tumor spread through air spaces Spatial characteristics Lung adenocarcinoma |
| title | The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features |
| title_full | The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features |
| title_fullStr | The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features |
| title_full_unstemmed | The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features |
| title_short | The correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma: focusing on pathological spatial features |
| title_sort | correlation of tertiary lymphoid structures with tumor spread through air spaces and prognosis in lung adenocarcinoma focusing on pathological spatial features |
| topic | Tertiary lymphoid structures Tumor spread through air spaces Spatial characteristics Lung adenocarcinoma |
| url | https://doi.org/10.1186/s12957-025-03751-z |
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