التفاصيل البيبلوغرافية
| العنوان: |
Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes |
| المؤلفون: |
Lilit Karapetyan, Hassan M. AbuShukair, Aofei Li, Andrew Knight, Ayah Nedal Al Bzour, Ian P. MacFawn, Zachary J. Thompson, Ann Chen, Xi Yang, Rebekah Dadey, Arivarasan Karunamurthy, Danielle Vargas De Stefano, Cindy Sander, Sheryl R. Kunning, Yana G. Najjar, Diwakar Davar, Jason J. Luke, William Gooding, Tullia C. Bruno, John M. Kirkwood, Walter J. Storkus |
| المصدر: |
Frontiers in Immunology, Vol 14 (2023) |
| بيانات النشر: |
Frontiers Media S.A., 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: |
tertiary lymphoid structure, lymphoid aggregate, melanoma, APRIL, TNFSF13, cytokine, Immunologic diseases. Allergy, RC581-607 |
| الوصف: |
BackgroundProinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics.MethodsLevels of TLS-kines in patients’ sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas melanoma cohort (TCGA-SKCM) and a Moffitt Melanoma cohort were used for tissue transcriptomic analyses. Associations between target analytes and survival outcomes, clinicopathological variables, and correlations between TLS-kines were statistically analyzed.ResultsSerum of 95 patients with melanoma were evaluated; 48 (50%) female, median age of 63, IQR 51-70 years. Serum levels of APRIL/TNFSF13 were positively correlated with levels of both CXCL10 and CXCL13. In multivariate analyses, high levels of serum APRIL/TNFSF13 were associated with improved event-free survival after adjusting for age and stage (HR = 0.64, 95% CI 0.43-0.95; p = 0.03). High expression of APRIL/TNFSF13 tumor transcripts was significantly associated with improved OS in TCGA-SKCM (HR = 0.69, 95% CI 0.52-0.93; p = 0.01) and in Moffitt Melanoma patients (HR = 0.51, 95% CI: 0.32-0.82; p = 0.006). Further incorporation of CXCL13 and CXCL10 tumor transcript levels in a 3-gene index revealed that high APRIL/CXCL10/CXCL13 expression was associated with improved OS in the TCGA SKCM cohort (HR = 0.42, 95% CI 0.19-0.94; p = 0.035). Melanoma differentially expressed genes positively associated with high APRIL/CXCL10/CXCL13 tumor expression were linked to tumor infiltration by a diverse array of proinflammatory immune cell types.ConclusionSerum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients exhibiting high coordinate expression of APRIL/CXCL10/CXCL13 transcripts in their tumors displayed superior OS. Further investigation of TLS-kine expression profiles related to clinical outcomes in larger cohort studies is warranted. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1171978/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2023.1171978 |
| URL الوصول: |
https://doaj.org/article/ebb1daa835334b64a636560bfe79e186 |
| رقم الانضمام: |
edsdoj.bb1daa835334b64a636560bfe79e186 |
| قاعدة البيانات: |
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