Evolutionary Action Score of TP53 Enhances the Prognostic Prediction for Stage I Lung Adenocarcinoma

Abstract

Stage I lung adenocarcinoma usually has a good prognosis after surgery. However, some patients do suffer disease recurrence during follow-up. Here, we report the prognostic value of evolutionary action score of TP53, which calculates the functional prediction of TP53, in patients with stage I lung adenocarcinoma. From January 2011 to August 2013, 83 patients with a complete follow-up history (36 with a disease recurrence and 47 without recurrence during follow-up) who were pathologically confirmed stage I lung adenocarcinoma were included. Whole-exome sequencing were performed on those paired tumor-normal specimens. Evolutionary action score of TP53 (EAp53) was calculated and patients were divided into groups according to their TP53 mutational status. Tumor mutational burden and survival analyses were performed to assess the prognostic value of EAp53. TP53 mutation was identified in 31 patients (37.3%). Of them, 11 were high-risk point mutations, 9 were low-risk point mutations, and 11 were truncating mutations. The high-risk group showed a poorer recurrence-free survival compared with the low-risk group (P = 0.046) and the wild-type group (P = 0.007). In multivariable analysis, the high-risk/truncating group showed a poorer recurrence-free survival (P = 0.007) and overall survival (P = 0.009) compared with the low-risk/wild-type group. Moreover, tumor mutational burden was higher in the high-risk/truncating group (P < 0.001). EAp53 is of prognostic value in patients with stage I lung adenocarcinoma. The mutational type of TP53 should be paid attention to when predicting the prognosis of patients with stage I lung adenocarcinoma.

Keywords: Evolutionary action score; Prognostic prediction; Stage I lung adenocarcinoma; TP53.