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Original Article | Open Access

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

Fan Kou1,*, Lei Wu1,*, Yan Guo1, Bailu Zhang1, Baihui Li1, Ziqi Huang1, Xiubao Ren1,2 ( ), Lili Yang1 ( )
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China

*These authors contributed equally to this work.

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Abstract

Objective

Lung cancer is the most common cause of cancer-related deaths worldwide. Somatic copy number alterations (SCNAs) have been used to predict responses to therapies in many cancers, including lung cancer. However, little is known about whether they are predictive of radiotherapy outcomes. We aimed to understand the prognostic value and biological functions of SCNAs.

Methods

We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy. Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response. Our results were validated in 20 patients with lung adenocarcinoma (LUAD) receiving radiotherapy.

Results

SCNAs were a better predictor of progression-free survival (PFS) in LUAD (P = 0.024) than in lung squamous carcinoma (P = 0.18) in patients treated with radiotherapy. Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD. Patients with stage Ⅰ cancer and low SCNA levels had longer PFS than those with high SCNA levels (P = 0.022). Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS. Additionally, high SCNA may activate the cell cycle pathway and induce tumorigenesis.

Conclusions

SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy, in combination with TNM, with the aim of predicting long-term PFS. Therefore, SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.

Keywords

lung cancerradiotherapyimmune infiltrationSCNAprogression-free survival

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Cancer Biology & Medicine
Volume 19 Issue 5,
May 2022
Pages 685-695
DOI: 10.20892/j.issn.2095-3941.2020.0728
Cite this article:
Kou F, Wu L, Guo Y, et al. Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy. Cancer Biology & Medicine, 2022, 19(5): 685-695. https://doi.org/10.20892/j.issn.2095-3941.2020.0728

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Received: 26 November 2020
Accepted: 19 May 2021
Published: 27 August 2021
©2022 Cancer Biology & Medicine.

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