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A microRNA signature for clinical outcomes of pediatric ALL patients treated with TPOG protocols
Ya-Hsuan Chang1, Shiann-Tarng Jou2,3, Ching-Tzu Yen4
1Institute of Statistical Science Academia Sinica Taipei, Taiwan.
Insights
MicroRNA (miRNA) expression predicts outcomes in childhood acute lymphoblastic leukemia (ALL). A novel miRNA signature effectively identified high-risk patients, improving prognostic accuracy for event-free survival and overall survival.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- MicroRNA (miRNA) expression is linked to clinical outcomes in pediatric acute lymphoblastic leukemia (ALL).
- Taiwan Pediatric Oncology Group (TPOG) protocols are used for treating pediatric ALL.
Purpose of the Study:
- To investigate the association between miRNA expression and clinical outcomes in pediatric ALL patients treated with TPOG protocols.
- To identify a miRNA signature for predicting prognosis in pediatric ALL.
Main Methods:
- Stem-loop quantitative real-time polymerase chain reaction miRNA arrays were used to measure miRNA expression in 60 pediatric ALL patients.
- Univariate Cox proportional hazards regression identified prognosis-related miRNAs.
- A risk score was calculated and validated in an independent cohort of 103 patients.
Main Results:
- Four prognosis-related miRNAs were identified and formed a risk score.
- The risk score significantly predicted event-free survival (EFS) and overall survival (OS) across training, testing, and validation cohorts.
- The risk score was the strongest predictor of EFS, outperforming clinical characteristics.
Conclusions:
- A miRNA signature is associated with clinical outcomes in childhood ALL patients treated with TPOG protocols.
- This miRNA signature may serve as a valuable prognostic biomarker for pediatric ALL.
Abstract:
MicroRNA (miRNA) expression is reportedly associated with clinical outcomes in childhood acute lymphoblastic leukemia (ALL). Here, we aimed at investigating whether miRNA expression is associated with clinical outcomes in pediatric ALL patients treated with the Taiwan Pediatric Oncology Group (TPOG) protocols. The expression of 397 miRNAs was measured using stem-loop quantitative real-time polymerase chain reaction miRNA arrays in 60 pediatric ALL patients treated with TPOG-ALL-93 or TPOG-ALL-97 VHR (very high-risk) protocols. In order to identify prognosis-related miRNAs, original cohort was randomly split into the training and testing cohort in a 2:1 ratio, and univariate Cox proportional hazards regression was applied to identify associations between event-free survival (EFS) and expressions of miRNAs. Four prognosis-related miRNAs were selected and validated in another independent cohort composed of 103 patients treated with the TPOG-ALL-2002 protocol. Risk score, including the impact of four prognosis-related miRNAs, was calculated for each patients, followed by grouping patients into the high or low risk-score groups. Irrespective of the training, testing, or validation cohort, risk-score group was significantly associated with EFS and overall survival (OS). Risk-score group combining with clinical characteristics including the age onset (≥10 years), white blood cell counts (≥100 × 109/L), cell type (T- or B-cell), sex, and risk groups of the treatment protocols were used as predictors of EFS using the multivariate Cox proportional hazards regression. Results showed that the risk-score group was the strongest predictor. In the validation cohort, hazard ratios (HRs) of the risk-score group were 7.06 (95% CI=1.93-25.84, p-value =0.003) and 14.03 (95% CI=3.34-59.04, p-value =0.003) for EFS and OS, respectively. High risk-score group had higher risk of having poor prognosis and risk of death than that in the low risk group. Accuracy of the prediction model for 5-year EFS could reach 0.76. For the prediction of 5-year OS, accuracy was 0.75. In conclusion, a miRNA signature was associated with clinical outcomes in childhood ALL patients treated with TPOG protocols and might be a suitable prognostic biomarker.
