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pmid:36704336

The gene signature of tertiary lymphoid structures within ovarian cancer predicts the prognosis and immunotherapy benefit.

Yue Hou · Sijing Qiao · Miao Li · Xue Han · Xuan Wei · Yingxin Pang · Hongluan Mao

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.1090640

Paper

complete

Experiment

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Data

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Analysis

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2026-11-01T19:01:16Z
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title
The gene signature of tertiary lymphoid structures within ovarian cancer predicts the prognosis and immunotherapy benefit.
doi
10.3389/fgene.2022.1090640
pmid
36704336
authors array · 7 items
[0]
Yue Hou
[1]
Sijing Qiao
[2]
Miao Li
[3]
Xue Han
[4]
Xuan Wei
[5]
Yingxin Pang
[6]
Hongluan Mao
journal
Frontiers in genetics
year
2022
abstract
Ovarian cancer (OC) has the lowest survival rate among gynecologic malignancies. Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers for tumor prognosis. However, the related gene signature of tertiary lymphoid structure in ovarian cancer was less understood. Therefore, this study first exhibited the organizational patterns of tertiary lymphoid structure by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival values of tertiary lymphoid structure and quantified tumor-infiltrating lymphocytes (CD20+ B cells and CD8+ T cells) in ovarian cancer patients. Secondly, we collected the genes involved in tertiary lymphoid structure from databases. By the univariate regression analysis, the tertiary lymphoid structure gene signature (CETP, CCR7, SELL, LAMP3, CCL19, CXCL9, CXCL10, CXCL11, and CXCL13) with prognostic value, characteristically of ovarian cancer, was constructed in the TCGA dataset and validated in the GSE140082 dataset. Thirdly, by performing CIBERSORT and Tumor Immune Dysfunction and Exclusion (TIDE) analysis, we found that the high expression of this gene signature was positively correlated with developed immune infiltration and reduced immune escape. The improved IPS score and application in the IMvigor210 dataset received PD-L1 proved the predictive value of immunotherapy for this gene signature. Furthermore, this signature showed a better correlation between tumor mutation burden and classical checkpoint genes. In conclusion, Tertiary lymphoid structure plays important role in tumor immunity and the gene signature can be evaluated as a biomarker for predicting prognosis and guiding immunotherapy in ovarian cancer.
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Differences in Overall Survival (OS) and Progression-Free Survival (PFS) between different groups were evaluated by Kaplan—Meier survival curve and verified by the log-rank test.
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Differences in Overall Survival (OS) and Progression-Free Survival (PFS) between different groups were evaluated by Kaplan—Meier survival curve and verified by the log-rank test.
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TLS-positive ovarian cancer patients showed superior 5-year overall survival and progression-free survival.
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sections[13] "3.2 The existence of TLSs represents a superior survival outcome" paragraph 2
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As portrayed in Figures 2A, B, the TLS-positive group performed the superior 5-year overall survival and progression-free survival (5-year-OS: p = .0078; 5-year-PFS: p = .041).
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TLS-positive ovarian cancer patients showed superior 5-year overall survival and progression-free survival.
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Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
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tiary lymphoid structure by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival v
[1]
re by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival values
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2 Materials and methods 2.2 HE and immunohistochemistry protocol The HE-stained sections were direct
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Differences in Overall Survival (OS) and Progression-Free Survival (PFS) between different groups were evaluated by Kaplan—Meier survival curve and verified by the log-rank test.
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Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers for tumor prognosis. However, the related gene signature of tertiary lymphoid structure in ovarian cancer was less understood. Therefore, this study first exhibited the organizational patterns of tertiary lymphoid structure by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival values of tertiary lymphoid structure and quantified tumor-infiltrating lymphocytes (CD20+ B cells and CD8+ T cells) in ovarian cancer patients. Secondly, we collected the genes involved in tertiary lymphoid structure from databases. By the univariate regression analysis, the tertiary lymphoid structure gene signature (CETP, CCR7, SELL, LAMP3, CCL19, CXCL9, CXCL10, CXCL11, and CXCL13) with prognostic value, characteristically of ovarian cancer, was constructed in the TCGA dataset and validated in the GSE140082 dataset. Thirdly, by performing CIBERSORT and Tumor Immune Dysfunction and Exclusion (TIDE) analysis, we found that the high expression of this gene signature was positively correlated with developed immune infiltration and reduced immune escape. The improved IPS score and application in the IMvigor210 dataset received PD-L1 proved the predictive value of immunotherapy for this gene signature. Furthermore, this signature showed a better correlation between tumor mutation burden and classical checkpoint genes. In conclusion, Tertiary lymphoid structure plays important role in tumor immunity and the gene signature can be evaluated as a biomarker for predicting prognosis and guiding immunotherapy in ovarian cancer.", "claims": [{"id": "claim-method", "statement": "Differences in Overall Survival (OS) and Progression-Free Survival (PFS) between different groups were evaluated by Kaplan—Meier survival curve and verified by the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36704336", "locator": "sections[10] \"2.8 Statistical analysis\" paragraph 2", "quote": "Differences in Overall Survival (OS) and Progression-Free Survival (PFS) between different groups were evaluated by Kaplan—Meier survival curve and verified by the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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