دورية أكاديمية

Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes

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: Karapetyan, Lilit, AbuShukair, Hassan M., Li, Aofei, Knight, Andrew, Al Bzour, Ayah Nedal, MacFawn, Ian P., Thompson, Zachary J., Chen, Ann, Yang, Xi, Dadey, Rebekah, Karunamurthy, Arivarasan, De Stefano, Danielle Vargas, Sander, Cindy, Kunning, Sheryl R., Najjar, Yana G., Davar, Diwakar, Luke, Jason J., Gooding, William, Bruno, Tullia C., Kirkwood, John M., Storkus, Walter J.
المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224
بيانات النشر: Frontiers Media SA
سنة النشر: 2023
المجموعة: Frontiers (Publisher - via CrossRef)
الوصف: Background Proinflammatory 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. Methods Levels 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. Results Serum 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. Conclusion Serum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients ...
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
DOI: 10.3389/fimmu.2023.1171978
DOI: 10.3389/fimmu.2023.1171978/full
الإتاحة: https://doi.org/10.3389/fimmu.2023.1171978Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.BC14842E
قاعدة البيانات: BASE