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

Bruce JP, Hui AB, Shi W, Perez-Ordonez B, Weinreb I, Xu W, Haibe-Kains B, Waggott DM, Boutros PC, O'Sullivan B, Waldron J, Huang SH, Chen EX, Gilbert R, Liu FF - Oncotarget (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

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.

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Related in: MedlinePlus

(A&B) Kaplan-Meier curves showing NPC patients dichotomized based on risk score in (A) the training cohort; and (B) the validation cohort. “High Risk” is defined as a RS ≥ the median in the training cohort, and “Low Risk” is defined as a RS < the median in the training cohort. (C) ROC AUCs across various time points demonstrating the ability of prognostic models generated using all possible combinations of 1, 2, 3, or 4 miRNAs from the 4-miRNA signature to predict distant relapse in NPC patients. RS, Risk Score; HR, Hazard Ratio; CI, Confidence Interval; ROC, receiver operating characteristic; AUC, Area Under the Curve.
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Figure 1: (A&B) Kaplan-Meier curves showing NPC patients dichotomized based on risk score in (A) the training cohort; and (B) the validation cohort. “High Risk” is defined as a RS ≥ the median in the training cohort, and “Low Risk” is defined as a RS < the median in the training cohort. (C) ROC AUCs across various time points demonstrating the ability of prognostic models generated using all possible combinations of 1, 2, 3, or 4 miRNAs from the 4-miRNA signature to predict distant relapse in NPC patients. RS, Risk Score; HR, Hazard Ratio; CI, Confidence Interval; ROC, receiver operating characteristic; AUC, Area Under the Curve.

Mentions: The RS was calculated for each patient in the Training cohort, allowing the patients to be dichotomized into either a “low risk” (< median), or a “high risk” (≥ median) group. A highly significant relationship was observed between the RS and the likelihood of DM whether the RS was treated as a continuous (Wald test; HR = 2.76, Scaled HR; 5.65; p = 2.8 × 10−5), or a binary (log-rank test: HR = 8.25; p = 8.0 × 10−4) variable (Figure 1A).


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

Bruce JP, Hui AB, Shi W, Perez-Ordonez B, Weinreb I, Xu W, Haibe-Kains B, Waggott DM, Boutros PC, O'Sullivan B, Waldron J, Huang SH, Chen EX, Gilbert R, Liu FF - Oncotarget (2015)

(A&B) Kaplan-Meier curves showing NPC patients dichotomized based on risk score in (A) the training cohort; and (B) the validation cohort. “High Risk” is defined as a RS ≥ the median in the training cohort, and “Low Risk” is defined as a RS < the median in the training cohort. (C) ROC AUCs across various time points demonstrating the ability of prognostic models generated using all possible combinations of 1, 2, 3, or 4 miRNAs from the 4-miRNA signature to predict distant relapse in NPC patients. RS, Risk Score; HR, Hazard Ratio; CI, Confidence Interval; ROC, receiver operating characteristic; AUC, Area Under the Curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414210&req=5

Figure 1: (A&B) Kaplan-Meier curves showing NPC patients dichotomized based on risk score in (A) the training cohort; and (B) the validation cohort. “High Risk” is defined as a RS ≥ the median in the training cohort, and “Low Risk” is defined as a RS < the median in the training cohort. (C) ROC AUCs across various time points demonstrating the ability of prognostic models generated using all possible combinations of 1, 2, 3, or 4 miRNAs from the 4-miRNA signature to predict distant relapse in NPC patients. RS, Risk Score; HR, Hazard Ratio; CI, Confidence Interval; ROC, receiver operating characteristic; AUC, Area Under the Curve.
Mentions: The RS was calculated for each patient in the Training cohort, allowing the patients to be dichotomized into either a “low risk” (< median), or a “high risk” (≥ median) group. A highly significant relationship was observed between the RS and the likelihood of DM whether the RS was treated as a continuous (Wald test; HR = 2.76, Scaled HR; 5.65; p = 2.8 × 10−5), or a binary (log-rank test: HR = 8.25; p = 8.0 × 10−4) variable (Figure 1A).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

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.

Show MeSH
Related in: MedlinePlus