Dataset Information

Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma.

ABSTRACT:

Purpose

Despite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients.

Methods and results

The expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways.

Conclusions

This 4-miRNA signature adds to the prognostic value of the current "gold standard" of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.

SUBMITTER: Bruce JP

PROVIDER: S-EPMC4414210 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Publications

Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma.

Bruce Jeff P JP Hui Angela B Y AB Shi Wei W Perez-Ordonez Bayardo B Weinreb Ilan I Xu Wei W Haibe-Kains Benjamin B Waggott Daryl M DM Boutros Paul C PC O'Sullivan Brian B Waldron John J Huang Shao Hui SH Chen Eric X EX Gilbert Ralph R Liu Fei-Fei FF

Oncotarget 20150201 6

<h4>Purpose</h4>Despite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC ...[more]

PMID: 25738365

Similar Datasets

Project description:BACKGROUND:The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC). METHODS:Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients. RESULTS:Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95%?CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95%?CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95%?CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed. CONCLUSIONS:The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.

Dataset Information

Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma.

Purpose

Methods and results

Conclusions

Publications

Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma.

Similar Datasets

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