Clinical Significance of PIK3CA Gene in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Sep 10

PMID 32908885

Citations 20

Authors

Yi Wang

Yan Wang

Jialong Li

Jue Li

Guowei Che

Affiliations

Soon will be listed here.

Abstract

Aim: To explore the clinicopathological and prognostic role of PIK3CA gene mutation and expression in non-small-cell lung cancer (NSCLC) patients.

Methods: A systematic and comprehensive literature search was conducted through EMBASE (via OVID), Web of Science, and PubMed. Relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to evaluate the relationship of the PIK3CA gene with clinicopathological parameters and the survival of NSCLC patients, respectively.

Results: A total of 13 studies involving 3908 patients were analyzed in our study. Only lymph node metastasis status had an association with PIK3CA mutation (RR = 2.823; 95% CI: 1.128-7.065; = 0.029). The results indicated that PICK3CA mutation was related with overall survival (OS) (HR = 1.55; 95% CI: 1.13-2.13; = 0.007), progression-free survival (PFS) (HR = 1.48; 95% CI: 1.06-2.08; = 0.023), and cancer-specific survival (CSS) (HR = 2.63; 95% CI: 1.00-6.92; = 0.005). Furthermore, PIK3CA high expression was more prevalent in NSCLC patients with smoking history (RR = 2.42; 95% CI: 1.04-5.61; = 0.040). However, no significant relation between PIK3CA expression and OS was found (HR = 0.80; 95% CI: 0.58-1.12; = 0.193).

Conclusion: PIK3CA mutation may affect lymph node metastasis and serve as a promising prognostic factor, and smoking may be related with PIK3CA high expression in NSCLC patients. However, more well-designed prospective researches are needed to verify the abovementioned findings.

Citing Articles

Successful conversion surgery following tislelizumab with chemotherapy in a patient with stage IIIC lung adenocarcinoma harboring RET fusions: A case report and review of the literature.

Tu D, Qu R, Wen F, Zhou Q, Liu Q, Huang L Exp Ther Med. 2025; 29(4):70.

PMID: 39991722 PMC: 11843209. DOI: 10.3892/etm.2025.12820.

Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.

Zhang B, Leung P, Cho W, Wong C, Wang D J Transl Med. 2025; 23(1):184.

PMID: 39953539 PMC: 11829425. DOI: 10.1186/s12967-025-06144-8.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Stalker M, Grady C, Watts A, Hwang W, Chandrasekhara K, Sun F JTO Clin Res Rep. 2025; 6(1):100765.

PMID: 39758601 PMC: 11699429. DOI: 10.1016/j.jtocrr.2024.100765.

Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma.

Cokpinar S, Erdogdu I, Orenay-Boyacioglu S, Boyacioglu O, Kahraman-Cetin N, Meteoglu I J Clin Med. 2024; 13(23).

PMID: 39685930 PMC: 11641866. DOI: 10.3390/jcm13237472.

Network pharmacology and molecular docking reveal the mechanism of action of Bergapten against non‑small cell lung cancer.

Chen Y, Fu Y, Zou H, Wang P, Xu Y, Xie Q Oncol Lett. 2024; 29(2):87.

PMID: 39677411 PMC: 11638938. DOI: 10.3892/ol.2024.14833.

References

Lau J, Ioannidis J, Schmid C . Quantitative synthesis in systematic reviews. Ann Intern Med. 1998; 127(9):820-6. DOI: 10.7326/0003-4819-127-9-199711010-00008. View

Thorpe L, Yuzugullu H, Zhao J . PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2014; 15(1):7-24. PMC: 4384662. DOI: 10.1038/nrc3860. View

Lu H, Qin J, Han N, Lei L, Xie F, Li C . , , , , and mutation in plasma of small cell lung cancer patients. Onco Targets Ther. 2018; 11:2217-2226. PMC: 5916454. DOI: 10.2147/OTT.S159612. View

Yu J, Bai H, Wang Z, Wei Z, Ding X, Duan J . PIK3CA mutation in Chinese patients with lung squamous cell carcinoma. Chin J Cancer Res. 2013; 25(4):416-22. PMC: 3752364. DOI: 10.3978/j.issn.1000-9604.2013.08.03. View

Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350:g7647. DOI: 10.1136/bmj.g7647. View

Sawa K, Koh Y, Kawaguchi T, Kambayashi S, Asai K, Mitsuoka S . PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer with chronic obstructive pulmonary disease: A comprehensive mutational analysis from a multi-institutional cohort. Lung Cancer. 2017; 112:96-101. DOI: 10.1016/j.lungcan.2017.07.039. View

Christensen T, Palshof J, Larsen F, Poulsen T, Hogdall E, Pfeiffer P . Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer. Acta Oncol. 2018; 57(8):1057-1062. DOI: 10.1080/0284186X.2018.1433322. View

Song Z, Yu X, Zhang Y . Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma. Cancer Med. 2016; 5(10):2694-2700. PMC: 5083721. DOI: 10.1002/cam4.852. View

Echeverria I, Liu Y, Gabelli S, Amzel L . Oncogenic mutations weaken the interactions that stabilize the p110α-p85α heterodimer in phosphatidylinositol 3-kinase α. FEBS J. 2015; 282(18):3528-42. PMC: 4573839. DOI: 10.1111/febs.13365. View

10.

McGowan M, Hoven A, Lund-Iversen M, Solberg S, Helland A, Hirsch F . PIK3CA mutations as prognostic factor in squamous cell lung carcinoma. Lung Cancer. 2016; 103:52-57. DOI: 10.1016/j.lungcan.2016.11.018. View

11.

Endoh H, Yatabe Y, Kosaka T, Kuwano H, Mitsudomi T . PTEN and PIK3CA expression is associated with prolonged survival after gefitinib treatment in EGFR-mutated lung cancer patients. J Thorac Oncol. 2007; 1(7):629-34. View

12.

Ludovini V, Bianconi F, Pistola L, Chiari R, Minotti V, Colella R . Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011; 6(4):707-15. DOI: 10.1097/JTO.0b013e31820a3a6b. View

13.

Vieira T, Antoine M, Ruppert A, Fallet V, Duruisseaux M, Giroux Leprieur E . Blood vessel invasion is a major feature and a factor of poor prognosis in sarcomatoid carcinoma of the lung. Lung Cancer. 2014; 85(2):276-81. DOI: 10.1016/j.lungcan.2014.06.004. View

14.

Toschi L, Finocchiaro G, Nguyen T, Skokan M, Giordano L, Gianoncelli L . Increased SOX2 gene copy number is associated with FGFR1 and PIK3CA gene gain in non-small cell lung cancer and predicts improved survival in early stage disease. PLoS One. 2014; 9(4):e95303. PMC: 3988173. DOI: 10.1371/journal.pone.0095303. View

15.

Chang S, Lai Y, Chang C, Huang L, Chen S, Tan K . Concomitant Genetic Alterations are Associated with Worse Clinical Outcome in EGFR Mutant NSCLC Patients Treated with Tyrosine Kinase Inhibitors. Transl Oncol. 2019; 12(11):1425-1431. PMC: 6700434. DOI: 10.1016/j.tranon.2019.07.008. View

16.

Zintzaras E, Ioannidis J . HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005; 21(18):3672-3. DOI: 10.1093/bioinformatics/bti536. View

17.

Wang Y, Wu Y, Li J, Li J, Che G . Clinicopathological and prognostic significance of thyroid transcription factor-1 expression in small cell lung cancer: A systemic review and meta-analysis. Pathol Res Pract. 2019; 215(12):152706. DOI: 10.1016/j.prp.2019.152706. View

18.

Tierney J, Stewart L, Ghersi D, Burdett S, Sydes M . Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8:16. PMC: 1920534. DOI: 10.1186/1745-6215-8-16. View

19.

Scheffler M, Bos M, Gardizi M, Konig K, Michels S, Fassunke J . PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget. 2014; 6(2):1315-26. PMC: 4359235. DOI: 10.18632/oncotarget.2834. View

20.

Wang L, Hu H, Pan Y, Wang R, Li Y, Shen L . 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. 2014; 9(2):e88291. PMC: 3922761. DOI: 10.1371/journal.pone.0088291. View