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. 2016 Dec 6;115(12):1513-1519.
doi: 10.1038/bjc.2016.370. Epub 2016 Nov 17.

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

Lishuang Qi  1 , Yang Li  1 , Yuan Qin  1 , Gengen Shi  1 , Tianhao Li  1 , Jiasheng Wang  1 , Libin Chen  1 , Yunyan Gu  1 , Wenyuan Zhao  1 , Zheng Guo  1   2
Affiliations

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

Lishuang Qi et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
The flowchart of this study. Combining the pathological response and 5-year survival data of 60 patients receiving platinum-based ACT in TCGA, we develop a REO-based signature. The signature was tested in an integrated independent data set and compared with three signatures developed based on patients' survival solely.
Figure 2
Figure 2
The K-means clustering of 60 patients receiving platinum-based ACT based on the top 50 differentially expressed genes between the responders and non-responders which were consistently classified by 3-GPS and their pathological response states.
Figure 3
Figure 3
The Kaplan–Meier curves of 5-year survival between different response groups predicted by 3-GPS in the testing data set. (A) All patients receiving platinum-based ACT. (B) Stage IB patients receiving platinum-based ACT. (C) Stage II–III patients receiving platinum-based ACT. (D) All patients not receiving ACT. (E) Stage IB patients not receiving ACT. (F) Stage II–III patients not receiving ACT.
Figure 4
Figure 4
The benefits of ACT in 5-year survival rate for the different response groups predicted by 3-GPS in the testing data set. (A) All patients in the predicted CR group. (B) Stage IB patients in the predicted CR group. (C) Stage II–III patients in the predicted CR group. (D) All patients in the predicted NR group. (E) Stage IB patients in the predicted NR group. (F) Stage II–III patients in the predicted NR group. The 5 ys rate represents 5-year survival rate.
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