An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

Background: For lung adenocarcinoma (LUAD) patients receiving platinum-based adjuvant chemotherapy (ACT), predictive signatures extracted from survival data solely are not directly associated with platinum response. Another limitation of reported signatures, commonly based on risk scores summarised from gene expressions, is that they could not be applied directly to samples measured by different laboratories due to experimental batch effects. Methods: Using 60 samples of LUAD patients receiving platinum-based ACT in TCGA, we pre-selected gene pairs whose within-samples relative expression orderings (REOs) were significantly associated with both pathological response and 5-year survival, from which we selected an optimal signature whose within-samples REOs could identify responders with improved 5-year survival rate. Results: A predictive signature consisting of three gene pairs was developed. In an independent data set integrated from five small data sets, the predicted responders had a significantly higher 5-year survival rate than the predicted non-responders if and only if they received platinum-based ACT (log-rank P =0.0006). The predicted responders showed a 22% absolute benefit of platinum-based ACT in 5-year survival rate compared with untreated patients (log-rank P =0.0019). Conclusions: The REO-based signature can individually predict response to platinum-based ACT with concordant survival benefit directly for LUAD samples measured by different laboratories.