+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

PIK3CA mutations frequently coexist with EGFR/KRAS mutations in non-small cell lung cancer and suggest poor prognosis in EGFR/KRAS wildtype subgroup



PIK3CA mutations frequently coexist with EGFR/KRAS mutations in non-small cell lung cancer and suggest poor prognosis in EGFR/KRAS wildtype subgroup



Plos One 9(2): E88291



PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer. Here we investigated PIK3CA gene alterations, the expression of core components of PI3K pathway, and evaluated their clinical importance in non-small cell lung cancer (NSCLC). Oncogenic mutations/rearrangements in PIK3CA, EGFR, KRAS, HER2, BRAF, AKT1 and ALK genes were detected in tumors from 1117 patients with NSCLC. PIK3CA gene copy number was examined by fluorescent in situ hybridization and the expression of PI3K p110 subunit alpha (PI3K p110α), p-Akt, mTOR, PTEN was determined by immunohistochemistry in PIK3CA mutant cases and 108 patients without PIK3CA mutation. PIK3CA mutation was found in 3.9% of squamous cell carcinoma and 2.7% of adenocarcinoma. Among 34 PIK3CA mutant cases, 17 tumors harbored concurrent EGFR mutations and 4 had KRAS mutations. PIK3CA mutation was significantly associated with high expression of PI3K p110α (p<0.0001), p-Akt (p = 0.024) and mTOR (p = 0.001), but not correlated with PIK3CA amplification (p = 0.463). Patients with single PIK3CA mutation had shorter overall survival than those with PIK3CA-EGFR/KRAS co-mutation or wildtype PIK3CA (p = 0.004). A significantly worse survival was also found in patients with PIK3CA mutations than those without PIK3CA mutations in the EGFR/KRAS wildtype subgroup (p = 0.043). PIK3CA mutations frequently coexist with EGFR/KRAS mutations. The poor prognosis of patients with single PIK3CA mutation in NSCLC and the prognostic value of PIK3CA mutation in EGFR/KRAS wildtype subgroup suggest the distinct mutation status of PIK3CA gene should be determined for individual therapeutic strategies in NSCLC.

(PDF emailed within 0-6 h: $19.90)

Accession: 054838075

Download citation: RISBibTeXText

PMID: 24533074

DOI: 10.1371/journal.pone.0088291


Related references

Optimization of patient selection for EGFR-TKIs in advanced non-small cell lung cancer by combined analysis of KRAS, PIK3CA, MET, and non-sensitizing EGFR mutations. Cancer ChemoTherapy and Pharmacology 69(5): 1289-1299, 2012

Gene mutations in squamous cell NSCLC: insignificance of EGFR, KRAS and PIK3CA mutations in prediction of EGFR-TKI treatment efficacy. Anticancer Research 33(4): 1705-1711, 2013

Next‑generation sequencing‑based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her‑2 and TP53 mutations in patients with non‑small cell lung cancer. Molecular Medicine Reports 18(2): 2191-2197, 2018

Assessment of the clinical application of detecting EGFR, KRAS, PIK3CA and BRAF mutations in patients with non-small cell lung cancer using next-generation sequencing. Scandinavian Journal of Clinical and Laboratory Investigation 76(5): 386-392, 2017

EGFR and HER2 genomic gain in recurrent non-small cell lung cancer after surgery: impact on outcome to treatment with gefitinib and association with EGFR and KRAS mutations in a Japanese cohort. Journal of Thoracic Oncology 4(3): 318-325, 2009

PD-1/PD-L1 expression in non-small-cell lung cancer and its correlation with EGFR/KRAS mutations. Cancer Biology and Therapy 17(4): 407-413, 2017

Roles of EGFR and KRAS Mutations in the Treatment Of Patients With Non-Small-Cell Lung Cancer. P and T 36(5): 263-279, 2011

EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients. Cancer Genetics and Cytogenetics 173(2): 107-113, 2007

Association of EGFR and KRAS mutations with expression of p-AKT, DR5 and DcR1 in non-small cell lung cancer. Neoplasma 64(2): 182-191, 2017

PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers. Lung Cancer 69(3): 279-283, 2011

Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clinical Cancer Research 18(4): 1167-1176, 2012

Should EGFR tyrosine kinase inhibitors be used in non-small cell lung cancer in the absence of EGFR mutations? No, EGFR TKIs should be reserved for patients with EGFR mutations. Clinical Advances in Hematology and Oncology 14(1): 41, 44-5, 2016

EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. Medical Oncology 31(8): 87, 2015

Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. Cancer ChemoTherapy and Pharmacology 77(3): 583-593, 2016

Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS. Oncology Reports 24(5): 1141-1146, 2011