Analysis of ultra-deep targeted sequencing reveals mutation burden is associated with gender and clinical outcome in lung adenocarcinoma
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Dakai Xiao1,2,3,*, Hui Pan1,2,*, Fuqiang Li4, Kui Wu4, Xin Zhang1,3, Jianxing He1,3
1Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
2Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
3Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, Guangzhou, China
4BGI-Shenzhen, Shenzhen, China
*These authors contributed equally to this work
Jianxing He, e-mail: [email protected]
Keywords: lung adenocarcinoma, targeted NGS sequencing, mutation burden
Received: December 21, 2015 Accepted: February 23, 2016 Published: March 19, 2016
Gender-associated difference in incidence and clinical outcomes of lung cancer have been established, but the biological mechanisms underlying these gender-associated differences are less studied. Recently we have characterized the genomic landscape of lung adenocarcinoma derived from Chinese population (Reference ). In this study we evaluated the clinical significance of mutation burden in lung adenocarcinoma and found that the male tumors harbored statistically greater burden of genetic alterations than female counterparts (Male median 3 (range 0–34) vs female median = 2 (0–24), male to female ratio = 1.636, 95% CI = 1.343–1.992) after adjustment of age at surgery, stage, smoking status. Kaplan-Meier survival analysis revealed that greater burden of genetic alterations was associated with worse overall survival. Moreover, multivariable analysis demonstrated mutation burden was an independent prognostic factor for the patients. Taken together, our analysis demonstrated gender disparity of mutation burden and their prognostic value in lung adenocarcinoma. This gender difference in mutation burden might provide an explanation for the distinct difference in the clinical outcomes between sexes in lung adenocarcinoma.
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