Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
February-2015 Volume 46 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2015 Volume 46 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma

  • Authors:
    • Yoshihito Iijima
    • Masahiro Seike
    • Rintaro Noro
    • Takayuki Ibi
    • Shingo Takeuchi
    • Iwao Mikami
    • Kiyoshi Koizumi
    • Jitsuo Usuda
    • Akihiko Gemma
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Graduate School of Medicine, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Thoracic Surgery, Aizu Chuo Hospital, Fukushima 965-8611, Japan
    Copyright: © Iijima et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 505-512
    |
    Published online on: November 10, 2014
       https://doi.org/10.3892/ijo.2014.2742
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA-/SOX2+) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA-/SOX2+ classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA-/SOX2+ cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA-/SOX2+ classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Lynch TJ, Bell DW, Sordella R, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Paez JG, Janne PA, Lee JC, et al: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Maemondo M, Inoue A, Kobayashi K, et al: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Mitsudomi T, Morita S, Yatabe Y, et al: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar

7 

Shaw AT, Kim DW, Nakagawa K, et al: Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 368:2385–2394. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Scagliotti GV, Parikh P, von Pawel J, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 26:3543–3551. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Sandler A, Gray R, Perry MC, et al: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 355:2542–2550. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP and Vansteenkiste J: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 350:351–360. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Winton T, Livingston R, Johnson D, et al: Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 352:2589–2597. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Douillard JY, Rosell R, De Lena M, et al: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association (ANITA)): a randomised controlled trial. Lancet Oncol. 7:719–727. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Olaussen KA, Fouret P and Kroemer G: ERCC1-specific immunostaining in non-small-cell lung cancer. N Engl J Med. 357:1559–1561. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Zheng Z, Chen T, Li X, Haura E, Sharma A and Bepler G: DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 356:800–808. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Friboulet L, Olaussen KA, Pignon JP, et al: ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med. 368:1101–1110. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Drilon A, Rekhtman N, Ladanyi M and Paik P: Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol. 13:e418–e426. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Paul KP, Adnan H, Lu W, Natasha R, Marc L and Mark GK: Multiplex testing for driver mutations in squamous cell carcinomas of the lung. J Clin Oncol. 30(Suppl): 75052012.

18 

The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 489:519–525. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Kim TJ, Lee JW, Song SY, et al: Increased expression of pAKT is associated with radiation resistance in cervical cancer. Br J Cancer. 94:1678–1682. 2006.PubMed/NCBI

20 

Yamamoto H, Shigematsu H, Nomura M, et al: PIK3CA mutations and copy number gains in human lung cancers. Cancer Res. 68:6913–6921. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Hussenet T, Dali S, Exinger J, et al: SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One. 5:e89602010. View Article : Google Scholar : PubMed/NCBI

22 

Hammerman PS, Sos ML, Ramos AH, et al: Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 1:78–89. 2011. View Article : Google Scholar

23 

McCarty KS Jr, Miller LS, Cox EB, Konrath J and McCarty KS Sr: Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 109:716–721. 1985.PubMed/NCBI

24 

Engelman JA, Luo J and Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 7:606–619. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Samuels Y, Wang Z, Bardelli A, et al: High frequency of mutations of the PIK3CA gene in human cancers. Science. 304:5542004. View Article : Google Scholar : PubMed/NCBI

26 

Karakas B, Bachman KE and Park BH: Mutation of the PIK3CA oncogene in human cancers. Br J Cancer. 94:455–459. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Campbell IG, Russell SE, Choong DY, et al: Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 64:7678–7681. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Massion PP, Kuo WL, Stokoe D, et al: Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway. Cancer Res. 62:3636–3640. 2002.PubMed/NCBI

29 

Kawano O, Sasaki H, Endo K, et al: PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer. 54:209–215. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Ji M, Guan H, Gao C, Shi B and Hou P: Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC). BMC Cancer. 11:1472011. View Article : Google Scholar : PubMed/NCBI

31 

Lu Y, Futtner C, Rock JR, et al: Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One. 5:e110222010. View Article : Google Scholar : PubMed/NCBI

32 

Tompkins DH, Besnard V, Lange AW, et al: Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells. PLoS One. 4:e82482009. View Article : Google Scholar : PubMed/NCBI

33 

Sholl LM, Long KB and Hornick JL: Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 18:55–61. 2010. View Article : Google Scholar

34 

Bass AJ, Watanabe H, Mermel CH, et al: SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 41:1238–1242. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Velcheti V, Schalper K, Yao X, et al: High SOX2 levels predict better outcome in non-small cell lung carcinomas. PLoS One. 8:e614272013. View Article : Google Scholar : PubMed/NCBI

36 

Brcic L, Sherer CK, Shuai Y, Hornick JL, Chirieac LR and Dacic S: Morphologic and clinicopathologic features of lung squamous cell carcinomas expressing Sox2. Am J Clin Pathol. 138:712–718. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Chen S, Xu Y, Chen Y, et al: SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells. PLoS One. 7:e363262012. View Article : Google Scholar : PubMed/NCBI

38 

Hussenet T and du Manoir S: SOX2 in squamous cell carcinoma: amplifying a pleiotropic oncogene along carcinogenesis. Cell Cycle. 9:1480–1486. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Toyooka S, Matsuo K, Shigematsu H, et al: The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non small cell lung cancer. Clin Cancer Res. 13:5763–5768. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Iijima Y, Seike M, Noro R, Ibi T, Takeuchi S, Mikami I, Koizumi K, Usuda J and Gemma A: Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma. Int J Oncol 46: 505-512, 2015.
APA
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I. ... Gemma, A. (2015). Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma. International Journal of Oncology, 46, 505-512. https://doi.org/10.3892/ijo.2014.2742
MLA
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I., Koizumi, K., Usuda, J., Gemma, A."Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma". International Journal of Oncology 46.2 (2015): 505-512.
Chicago
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I., Koizumi, K., Usuda, J., Gemma, A."Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma". International Journal of Oncology 46, no. 2 (2015): 505-512. https://doi.org/10.3892/ijo.2014.2742
Copy and paste a formatted citation
x
Spandidos Publications style
Iijima Y, Seike M, Noro R, Ibi T, Takeuchi S, Mikami I, Koizumi K, Usuda J and Gemma A: Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma. Int J Oncol 46: 505-512, 2015.
APA
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I. ... Gemma, A. (2015). Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma. International Journal of Oncology, 46, 505-512. https://doi.org/10.3892/ijo.2014.2742
MLA
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I., Koizumi, K., Usuda, J., Gemma, A."Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma". International Journal of Oncology 46.2 (2015): 505-512.
Chicago
Iijima, Y., Seike, M., Noro, R., Ibi, T., Takeuchi, S., Mikami, I., Koizumi, K., Usuda, J., Gemma, A."Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma". International Journal of Oncology 46, no. 2 (2015): 505-512. https://doi.org/10.3892/ijo.2014.2742
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team