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12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

ABSTRACT: We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20? B cell follicles with prominent areas of CD3? T cells (both CD4? and CD8? subsets). CD86?, but not FoxP3?, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

SUBMITTER: Messina JL

PROVIDER: S-EPMC3479449 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

Messina Jane L JL Fenstermacher David A DA Eschrich Steven S Qu Xiaotao X Berglund Anders E AE Lloyd Mark C MC Schell Michael J MJ Sondak Vernon K VK Weber Jeffrey S JS Mulé James J JJ

Scientific reports 20121024

We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20⁺ B cell follicles with prominent areas of CD3⁺ T cells (both CD4⁺ a ...[more]

PMID: 23097687

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Project description:Background & aimsPancreatic ductal adenocarcinomas (PDACs) frequently metastasize to the lymph nodes; strategies are needed to identify patients at highest risk for lymph node metastases. We performed genome-wide expression profile analyses of PDAC specimens, collected during surgery or endoscopic ultrasound-guided fine-need aspiration (EUS-FNA), to identify a microRNA (miRNA) signature associated with metastasis to lymph nodes.MethodsFor biomarker discovery, we analyzed miRNA expression profiles of primary pancreatic tumors from 3 public data sets (The Cancer Genome Atlas, GSE24279, and GSE32688). We then analyzed 157 PDAC specimens (83 from patients with lymph node metastases and 74 without) from Japan, collected from 2001 through 2017, for the training cohort and 107 PDAC specimens (63 from patients with lymph node metastases and 44 without) from a different medical center in Japan, from 2002 through 2016, for the validation cohort. We also analyzed samples collected by EUS-FNA before surgery from 47 patients (22 patients with lymph node metastases and 25 without; 17 for the training cohort and 30 from the validation cohort) and 62 specimens before any treatment from patients who received neoadjuvant chemotherapy (9 patients with lymph node metastasis and 53 without) for additional validation. Multivariate logistic regression analyses were used to evaluate the statistical differences in miRNA expression between patients with vs without metastases.ResultsWe identified an miRNA expression pattern associated with diagnosis of PDAC metastasis to lymph nodes. Using logistic regression analysis, we optimized and trained a 6-miRNA risk prediction model for the training cohort; this model discriminated patients with vs without lymph node metastases with an area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.77-0.89). In the validation cohort, the model identified patients with vs without lymph node metastases with an AUC of 0.73 (95% CI, 0.64-0.81). In EUS-FNA biopsy samples, the model identified patients with vs without lymph node metastases with an AUC of 0.78 (95% CI, 0.63-0.89). The miRNA expression pattern was an independent predictor of PDAC metastasis to lymph nodes in the validation cohort (odds ratio, 17.05; 95% CI, 2.43-119.57) and in the EUS-FNA cohort (95% CI, 0.65-0.87).ConclusionsUsing data and tumor samples from 3 independent cohorts, we identified an miRNA signature that identifies patients at risk for PDAC metastasis to lymph nodes. The signature has similar levels of accuracy in the analysis of resected tumor specimens and EUS-FNA biopsy specimens. This model might be used to select treatment and management strategies for patients with PDAC.

Dataset Information

12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

Publications

12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

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