PIK3CA gene mutation associated with poor prognosis of lung adenocarcinoma
Lina Zhang,1,* Lei Shi,2,* Xiaoting Zhao,1 Yue Wang,1 Wentao Yue1
1Department of Molecular and Cellular Biology, Beijing Chest Hospital, Capital Medical University, Beijing TB and Thoracic Tumor Research Institute, Beijing, People's Republic of China; 2Department of Hepatobiliary Surgery, the First Affiliated Hospital Medical School of Xi'an Jiaotong University, Xi'an, People's Republic of China
*These authors contributed equally to this work
Purpose: PIK3CA gene mutations have been detected in many malignancies, but the frequency of different mutations and their role in the carcinogenesis of lung adenocarcinoma are still unclear. The purpose of this study was to explore the clinical pathological impact and prognostic implications of PIK3CA mutations in lung adenocarcinoma.
Methods: Five common PIK3CA mutations (E542K, E545K, and E545D mutation in exon 9, H1047R and H1047L mutation in exon 20) were detected by amplification refractory mutation system (ARMS) allele-specific polymerase chain reaction (PCR), in 122 patients with lung adenocarcinoma. The relationships were studied between these mutations and various clinicopathologic variables (age, lymph node status, distant metastasis, clinicopathologic stage, smoking status, and progression-free survival).
Results: In total, 25 mutations were identified, of which 24 mutations were clustered in exon 20, and one mutation in exon 9. The most common mutations were H1047R (18 out of the 122 patients, 14.8%) in exon 20. PIK3CA-mutated tumors were more frequently found in patients with lymph node positive metastasis status (P < 0.05). There was no significant association between PIK3CA mutations and age, distant metastasis, smoking status, or clinicopathologic stage. However, mutations were found less frequently in the early clinicopathologic stage patients (six in 50 cases, 12%) than in advanced stage (19 in 72 cases, 26.4%). Higher frequency of H1047R mutations was associated with poor prognosis, and this association reached statistical significance (P < 0.05).
Conclusion: Our data indicate that the PIK3CA mutations H1047R and H1047L are significant genetic alterations in lung adenocarcinoma. Among lung adenocarcinoma patients who underwent curative resection, PIK3CA mutations were associated with shorter progression-free survival. Our findings demonstrated a significant role of PIK3CA in lung adenocarcinoma.
Keywords: Phosphatidylinositol-3-kinase catalytic subunit (PIK3CA); H1047R mutation; Cancer; Lung neoplasms