Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study
Background Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with cancer prognosis and therapeutic response. However, the immunological pattern of a high peritumoral TLS (pTLS) density and its clinical potential in hepatocellular carcinoma (HCC) remain poor. T...
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009879.full |
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| author | Juan Chen Xiong Chen Kai Fu Lan Zhou Shichao Long Mengsi Li Linhui Zhong Aerzuguli Abudulimu Wenguang Liu Deng Pan Ganmian Dai Yigang Pei Wenzheng Li |
| author_facet | Juan Chen Xiong Chen Kai Fu Lan Zhou Shichao Long Mengsi Li Linhui Zhong Aerzuguli Abudulimu Wenguang Liu Deng Pan Ganmian Dai Yigang Pei Wenzheng Li |
| author_sort | Juan Chen |
| collection | DOAJ |
| description | Background Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with cancer prognosis and therapeutic response. However, the immunological pattern of a high peritumoral TLS (pTLS) density and its clinical potential in hepatocellular carcinoma (HCC) remain poor. This study aimed to elucidate biological differences related to pTLS density and develop a radiomic classifier for predicting pTLS density in HCC, offering new insights for clinical diagnosis and treatment.Methods Spatial transcriptomics (n=4) and RNA sequencing data (n=952) were used to identify critical regulators of pTLS density and evaluate their prognostic significance in HCC. Baseline MRI images from 660 patients with HCC who had undergone surgery treatment between October 2015 and January 2023 were retrospectively recruited for model development and validation. This included training (n=307) and temporal validation (n=76) cohorts from Xiangya Hospital, and external validation cohorts from three independent hospitals (n=277). Radiomic features were extracted from intratumoral and peritumoral regions of interest and analyzed using machine learning algorithms to develop a predictive classifier. The classifier’s performance was evaluated using the area under the curve (AUC), with prognostic and predictive value assessed across four independent cohorts and in a dual-center outcome cohort of 41 patients who received immunotherapy.Results Patients with HCC and a high pTLS density experienced prolonged median overall survival (p<0.05) and favorable immunotherapy response (p=0.03). Moreover, immune infiltration by mature B cells was observed in the high pTLS density region. Spatial pseudotime analysis and immunohistochemistry staining revealed that expansion of pTLS in HCC was associated with elevated CXCL9 and CXCL10 co-expression. We developed an optimal radiomic-based classifier with excellent discrimination for predicting pTLS density, achieving an AUC of 0.91 (95% CI 0.87, 0.94) in the external validation cohort. This classifier also exhibited promising stratification ability in terms of overall survival (p<0.01), relapse-free survival (p<0.05), and immunotherapy response (p<0.05).Conclusion We identified key regulators of pTLS density in patients with HCC and proposed a non-invasive radiomic classifier capable of assisting in stratification for prognosis and treatment. |
| format | Article |
| id | doaj-art-b7ab78504bbd4e9b80c11a401d580ff3 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b7ab78504bbd4e9b80c11a401d580ff32024-12-17T23:10:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009879Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter studyJuan Chen0Xiong Chen1Kai Fu2Lan Zhou3Shichao Long4Mengsi Li5Linhui Zhong6Aerzuguli Abudulimu7Wenguang Liu8Deng Pan9Ganmian Dai10Yigang Pei11Wenzheng Li12Department of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaInstitute of Molecular Precision Medicine, Xiangya Hospital Central South University, Changsha, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Nuclear Medicine, Hainan Cancer Hospital of Hainan Medical University, Haikou, Hainan, ChinaDepartment of Radiology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Radiology, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, ChinaBackground Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with cancer prognosis and therapeutic response. However, the immunological pattern of a high peritumoral TLS (pTLS) density and its clinical potential in hepatocellular carcinoma (HCC) remain poor. This study aimed to elucidate biological differences related to pTLS density and develop a radiomic classifier for predicting pTLS density in HCC, offering new insights for clinical diagnosis and treatment.Methods Spatial transcriptomics (n=4) and RNA sequencing data (n=952) were used to identify critical regulators of pTLS density and evaluate their prognostic significance in HCC. Baseline MRI images from 660 patients with HCC who had undergone surgery treatment between October 2015 and January 2023 were retrospectively recruited for model development and validation. This included training (n=307) and temporal validation (n=76) cohorts from Xiangya Hospital, and external validation cohorts from three independent hospitals (n=277). Radiomic features were extracted from intratumoral and peritumoral regions of interest and analyzed using machine learning algorithms to develop a predictive classifier. The classifier’s performance was evaluated using the area under the curve (AUC), with prognostic and predictive value assessed across four independent cohorts and in a dual-center outcome cohort of 41 patients who received immunotherapy.Results Patients with HCC and a high pTLS density experienced prolonged median overall survival (p<0.05) and favorable immunotherapy response (p=0.03). Moreover, immune infiltration by mature B cells was observed in the high pTLS density region. Spatial pseudotime analysis and immunohistochemistry staining revealed that expansion of pTLS in HCC was associated with elevated CXCL9 and CXCL10 co-expression. We developed an optimal radiomic-based classifier with excellent discrimination for predicting pTLS density, achieving an AUC of 0.91 (95% CI 0.87, 0.94) in the external validation cohort. This classifier also exhibited promising stratification ability in terms of overall survival (p<0.01), relapse-free survival (p<0.05), and immunotherapy response (p<0.05).Conclusion We identified key regulators of pTLS density in patients with HCC and proposed a non-invasive radiomic classifier capable of assisting in stratification for prognosis and treatment.https://jitc.bmj.com/content/12/12/e009879.full |
| spellingShingle | Juan Chen Xiong Chen Kai Fu Lan Zhou Shichao Long Mengsi Li Linhui Zhong Aerzuguli Abudulimu Wenguang Liu Deng Pan Ganmian Dai Yigang Pei Wenzheng Li Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study Journal for ImmunoTherapy of Cancer |
| title | Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study |
| title_full | Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study |
| title_fullStr | Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study |
| title_full_unstemmed | Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study |
| title_short | Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study |
| title_sort | spatial patterns and mri based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma a multicenter study |
| url | https://jitc.bmj.com/content/12/12/e009879.full |
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