Nomogram integrating gene expression signatures with clinicopathological features to predict survival in operable NSCLC: a pooled analysis of 2164 patients

Jian Wu, Lizhi Zhou, Lixia Huang, Jincui Gu, Shaoli Li, Baomo Liu, Jinlun Feng, Yanbin Zhou

The current tumor-node-metastasis (TNM) staging system is insufficient to predict outcome of patients with operable Non-Small Cell Lung Cancer (NSCLC) owing to its phenotypic and genomic heterogeneity. Integrating genomic signatures with clinicopathological factors may provide more detailed evaluation of prognosis. All 2164 clinically annotated NSCLC samples (1326 in the training set and 838 in the validation set) with corresponding microarray data from 17 cohorts were pooled to develop and validate a clinicopathologic-genomic nomogram based on Cox regression model. Two computational methods were applied to these samples to capture expression pattern of genomic signatures representing biological statuses. Model performance was measured by the concordance index (C-index) and calibration plot. Risk group stratification was proposed for the nomogram. Multivariable analysis of the training set identified independent factors including age, TNM stage, combined prognostic classifier, non-overlapping signature, and the ratio of neutrophil to plasma cells. The C-index of the nomogram for predicting survival was statistically superior to that of the TNM stage (training set, 0.686 vs 0.627, respectively; P < .001; validation set, 0.689 vs 0.638, respectively; P < .001). The calibration plots showed that the predicted 1-, 3- and 5-year survival probabilities agreed well with the actual observations. Stratifying patients into three risk groups detected significant differences among survival curves. These findings offer preliminary evidence that genomic data provide independent and complementary prognostic information and incorporation of this information can refine prognosis in NSCLC. Prospective studies are required to further explore the value of this composite model for prognostic stratification and tailored therapeutic strategies.