YuXuan Zhang,1,2,* Yuhong Shen,3,* Jiayuan Wu,2 Jun Zhang,4 Chenxi Cao,5 Juanfen Mo,2 Yi Bao2,5 

1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2The Key Laboratory, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Transfusion Center, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4The Department of Thoracic Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 5The Department of Oncology, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Bao, The Key Laboratory, The Department of Oncology, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Zhejiang, People’s Republic of China, 314000, Email ybao2011@zjxu.edu.cn Juanfen Mo, The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, 1518 Huancheng North Road, Jiaxing, Zhejiang, People’s Republic of China, 314000, Email mojuanfen@163.com

Objective: PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center.
Materials and Methods: We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients.
Results: Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G > A, E545K, and c.1624G > A, E542K) and exon 20 (c.3140A > G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301– 0.896; P < 0.05).
Conclusion: PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.

Keywords: co-occurring mutation, non-small cell lung cancer, PIK3CA, The Cancer Genome Atlas, Memorial Sloan Kettering Cancer Center