TERT Mutations in Non-Small Cell Lung Cancer: Clinicopathologic Features and Prognostic Implications

Abstract

Introduction: The associations between the clinical characteristics of non-small cell lung cancer (NSCLC) and mutations in telomerase reverse transcriptase (TERT) gene remain unclear. In this study, we used next-generation sequencing (NGS) to investigate the incidence rate and clinical correlates of TERT mutations in patients with NSCLC.

Methods: In total, 283 tumor samples from patients with NSCLC were tested using an NGS panel from September 2017 to May 2020. The genetic testing results and clinical data of all patients were collected.

Results: TERT mutations were found in 30 patients, which were significantly associated with age, smoking history, sex, and metastasis (P < 0.05). Survival analyses showed that patients who carried TERT mutations had a poorer prognosis. Of the 30 TERT-mutation carriers, 17 harbored epidermal growth factor receptor (EGFR) mutations, which were significantly associated with sex, histopathology type, and metastasis (P < 0.05; overall survival [OS], 21 months; 95% confidence interval [CI], 8.153-33.847 months). Three TERT mutation patients harbored Kirsten rat sarcoma virus (KRAS) mutations, which were significantly associated with metastasis risk (P < 0.05), KRAS mutations carriers had a worse prognosis, with an OS of 10 months (95% CI, 8.153-33.847 months). Multivariate Cox regression analyses showed that age, cancer stage, and TERT mutation carrier status were independent risk factors for NSCLC, and the TERT mutation was 2.731 times higher than that without TERT mutation (95% CI, 1.689-4.418, P < 0.001).

Conclusions: TERT mutations were present in 11% of patients with NSCLC. TERT mutations were associated with age, smoking history, sex, and distant metastasis. Co-mutations in TERT and EGFR/KRAS indicated a poor prognosis. The co-mutations of TERT and EGFR differed according to sex, histopathology type, and metastasis, whereas TERT and KRAS co-mutations were only associated with patient metastasis. Age, cancer stage, and TERT mutation carrier status were independent risk factors for poor prognosis in patients with NSCLC.

Keywords: Non–small cell lung cancer; TERT; co-mutation; prognosis.

Figure 1.

Overall survival for 283 patients with non–small cell lung cancer. (A) Kaplan-Meier (K-M) curve of TERT mutant and wild-type OS shows their association (P = 0.0061). (B) K-M curves of OS under different mutation states of TERT and EGFR. There were significant differences in OS (P = 0.0056) among the four groups in NSCLC. (C) K-M curves of OS under different mutation states of TERT and KRAS shows significant differences in OS (P = 0.0012) among the four groups in NSCLC. EGFR indicates epidermal growth factor receptor; EGFR^m, EGFR mutant; EGFR^w, EGFR wild-type; K-M, Kaplan Meier; KRAS, Kirsten rat sarcoma virus; KRAS^m, KRAS mutant; KRAS^w, KRAS wild-type; NSCLC, non–small cell lung cancer; OS, overall survival; TERT, telomerase reverse transcriptase; TERT^m, TERT mutant; TERT^w, TERT wild-type.