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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October 2014 Volume 8 Issue 4

Full Size Image

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
October 2014 Volume 8 Issue 4

Full Size Image

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

Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer

  • Authors:
    • Jing Li
    • Lin‑Lin Yin
    • Ke‑Li Su
    • Gang‑Feng Zhang
    • Jing Wang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Fourth People's Hospital of Jinan, Jinan, Shandong 250031, P.R. China
  • Pages: 1543-1550
    |
    Published online on: July 14, 2014
       https://doi.org/10.3892/ol.2014.2350
  • 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

Prognostic markers for colorectal cancer (CRC) have not yet been fully investigated. Phosphatase and tensin homolog (PTEN), p27 and Cyclin D1 play significant roles in tumorigenesis and cell cycle regulation, and therefore require evaluation for their prognostic value in this disease. The aim of the present study was to assess the prognostic value of the single and combined expression of PTEN, p27 and Cyclin D1 in CRC patients. Protein expression levels of PTEN, p27 and Cyclin D1 were examined by immunohistochemistry from 61 patients with CRC in either stage Ⅱ or Ⅲ. In the CRC tissues, the frequencies of PTEN(‑), p27(‑) and Cyclin D1(+) expression were 42.62% (26/61), 32.79% (20/61) and 45.90% (28/61), respectively. Depletion of PTEN and p27 was more common with respect to stage Ⅲ, low grade and lymph node metastasis compared with stage Ⅱ, moderate grade and no lymph node metastasis (P<0.05). Cyclin D1‑positive expression was frequently detected in CRC of stage Ⅲ, with lymph node metastasis and deeper invasion (P<0.05). The depletion of PTEN was significantly correlated with the loss of p27 (P<0.001) and with the increased expression of Cyclin D1 (P<0.001). PTEN(‑) and/or p27(‑) expression was significantly correlated with Cyclin D1(+) expression (P<0.05). Combined PTEN(‑)/p27(‑)/Cyclin D1(+) expression was correlated with a significant decrease in overall survival time (P<0.05). Combined p27(‑) and Cyclin D1(+) expression indicated a worse overall survival time than other combined expression patterns. These findings indicate that the single expression of PTEN(‑), p27(‑) and Cyclin D1(+) and the combined detection of p27(‑) and Cyclin D1(+) may be used as prognostic markers for overall survival time in CRC.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Wang N, Zhu WX, Xing XM, et al: Time trends of cancer incidence in urban Beijing, 1998–2007. Chin J Cancer Res. 23:15–20. 2011.

2 

Goodwin RA and Asmis TR: Overview of systemic therapy for colorectal cancer. Clin Colon Rectal Surg. 22:251–256. 2009.

3 

Quasar Collaborative Group. Gray R, Barnwell J, et al: Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 370:2020–2029. 2007.

4 

André T, Boni C, Navarro M, et al: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 27:3109–3116. 2009.

5 

Voorneveld PW, Jacobs RJ, De Miranda NF, et al: Evaluation of the prognostic value of pSMAD immunohistochemistry in colorectal cancer. Eur J Cancer Prev. 22:420–424. 2013.

6 

Saito S, Okabe H, Watanabe M, et al: CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. Oncol Rep. 29:1570–1578. 2013.

7 

Bahnassy AA, Zekri AR, Alam El-Din HM, et al: The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma. J Egypt Natl Canc Inst. 18:292–302. 2006.

8 

Taghavi N, Biramijamal F, Sotoudeh M, et al: p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in esophageal squamous cell carcinoma. BMC Cancer. 10:1382010.

9 

Bartkova J, Rajpert-De Meyts E, Skakkebaek NE, et al: Deregulation of the G1/S-phase control in human testicular germ cell tumours. APMIS. 111:252–266. 2003.

10 

Macaluso M, Montanari M, Cinti C and Giordano A: Modulation of cell cycle components by epigenetic and genetic events. Semin Oncol. 32:452–457. 2005.

11 

Gordon GM, Zhang T, Zhao J and Du W: Deregulated G1-S control and energy stress contribute to the synthetic-lethal interactions between inactivation of RB and TSC1/TSC2. J Cell Sci. 126:2004–2013. 2013.

12 

Sun CH, Chang YH and Pan CC: Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder. Histopathology. 58:1054–1063. 2011.

13 

Perisanidis C, Perisanidis B, Wrba F, et al: Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 in oral and oropharyngeal squamous cell carcinoma. J Oral Pathol Med. 41:40–46. 2012.

14 

Strimpakos AS, Karapanagiotou EM, Saif MW and Syrigos KN: The role of mTOR in the management of solid tumors: an overview. Cancer Treat Rev. 35:148–159. 2009.

15 

Asano T, Yao Y, Zhu J, et al: The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells. Oncogene. 23:8571–8580. 2004.

16 

Jin C, Wang A, Chen J, et al: Relationship between expression and prognostic ability of PTEN, STAT3 and VEGF-C in colorectal cancer. Exp Ther Med. 4:633–639. 2012.

17 

Ghiţă C, Vîlcea ID, Dumitrescu M, et al: The prognostic value of the immunohistochemical aspects of tumor suppressor genes p53, bcl-2, PTEN and nuclear proliferative antigen Ki-67 in resected colorectal carcinoma. Rom J Morphol Embryol. 53:549–556. 2012.

18 

Al-Maghrabi J, Al-Ahwal M, Buhmeida A, et al: Expression of cell cycle regulators p21 and p27 as predictors of disease outcome in colorectal carcinoma. J Gastrointest Cancer. 43:279–287. 2012.

19 

Zlobec I, Minoo P, Baumhoer D, et al: Multimarker phenotype predicts adverse survival in patients with lymph node-negative colorectal cancer. Cancer. 112:495–502. 2008.

20 

Wang MT, Chen G, An SJ, et al: Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma. Dis Esophagus. 25:664–670. 2012.

21 

Sugimoto M, Martin N, Wilks DP, et al: Activation of cyclin D1-kinase in murine fibroblasts lacking both p21(Cip1) and p27(Kip1). Oncogene. 21:8067–8074. 2002.

22 

Mao Y, Li Z, Lou C and Zhang Y: Expression of phosphorylated Stat5 predicts expression of cyclin D1 and correlates with poor prognosis of colonic adenocarcinoma. Int J Colorectal Dis. 26:29–35. 2011.

23 

Belt EJ, Brosens RP, Delis-van Diemen PM, et al: Cell cycle proteins predict recurrence in stage II and III colon cancer. Ann Surg Oncol. 19(Suppl 3): S682–S692. 2012.

24 

Weng LP, Brown JL and Eng C: PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum Mol Genet. 10:599–604. 2001.

25 

Lan YT, Yang SH, Chang SC, et al: Analysis of the seventh edition of American Joint Committee on colon cancer staging. Int J Colorectal Dis. 27:657–653. 2011.

26 

Bertagnolli MM, Warren RS, Niedzwiecki D, et al: p27Kip1 in stage III colon cancer: implications for outcome following adjuvant chemotherapy in cancer and leukemia group B protocol 89803. Clin Cancer Res. 15:2116–2122. 2009.

27 

Li D, Zhang Y, Xie Y, et al: Enhanced tumor suppression by adenoviral PTEN gene therapy combined with cisplatin chemotherapy in small-cell lung cancer. Cancer Gene Ther. 20:251–259. 2013.

28 

Zhu L, Loo WT and Louis WC: PTEN and VEGF: possible predictors for sentinel lymph node micro-metastasis in breast cancer. Biomed Pharmacother. 61:558–561. 2007.

29 

Hsu CP, Kao TY, Chang WL, et al: Clinical significance of tumor suppressor PTEN in colorectal carcinoma. Eur J Surg Oncol. 37:140–147. 2011.

30 

Jung SM, Park SS, Kim WJ and Moon SK: Ras/ERK1 pathway regulation of p27KIP1-mediated G1-phase cell-cycle arrest in cordycepin-induced inhibition of the proliferation of vascular smooth muscle cells. Eur J Pharmacol. 681:15–22. 2012.

31 

Tsutsui S, Inoue H, Yasuda K, et al: Inactivation of PTEN is associated with a low p27Kip1 protein expression in breast carcinoma. Cancer. 104:2048–2053. 2005.

32 

Zolota VG, Tzelepi VN, Leotsinidis M, et al: Histologic-type specific role of cell cycle regulators in non-small cell lung carcinoma. J Surg Res. 164:256–265. 2010.

33 

Shapira M, Ben-Izhak O, Linn S, et al: The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma. Cancer. 103:1336–1346. 2005.

34 

Engin H, Baltali E, Güler N, et al: Expression of PTEN, cyclin D1, P27/KIP1 in invasive ductal carcinomas of the breast and correlation with clinicopathological parameters. Bull Cancer. 93:E21–E26. 2006.

35 

Ioachim E: Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21waf1/cip1, p27kip1 in colorectal carcinoma: correlation with other cell cycle regulators (pRb, p53 and Ki-67 and PCNA) and clinicopathological features. Int J Clin Pract. 62:1736–1743. 2008.

36 

Hwang TS, Han HS, Hong YC, et al: Prognostic value of combined analysis of cyclin D1 and estrogen receptor status in breast cancer patients. Pathol Int. 53:74–80. 2003.

37 

Sherr CJ and Roberts JM: CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999.

38 

Halvorsen OJ, Haukaas SA and Akslen LA: Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer. Clin Cancer Res. 9:1474–1479. 2003.

39 

Fiano V, Ghimenti C, Imarisio S, et al: pAkt, cyclin D1 and p27/Kip. 1 in glioblastomas with and without EGFR amplification and PTEN mutation. Anticancer Res. 24:2643–2647. 2004.

40 

Ye YW, Wu JH, Wang CM, et al: Sox17 regulates proliferation and cell cycle during gastric cancer progression. Cancer Lett. 307:124–131. 2011.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li J, Yin LL, Su KL, Zhang GF and Wang J: Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer. Oncol Lett 8: 1543-1550, 2014.
APA
Li, J., Yin, L., Su, K., Zhang, G., & Wang, J. (2014). Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer. Oncology Letters, 8, 1543-1550. https://doi.org/10.3892/ol.2014.2350
MLA
Li, J., Yin, L., Su, K., Zhang, G., Wang, J."Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer". Oncology Letters 8.4 (2014): 1543-1550.
Chicago
Li, J., Yin, L., Su, K., Zhang, G., Wang, J."Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer". Oncology Letters 8, no. 4 (2014): 1543-1550. https://doi.org/10.3892/ol.2014.2350
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Yin LL, Su KL, Zhang GF and Wang J: Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer. Oncol Lett 8: 1543-1550, 2014.
APA
Li, J., Yin, L., Su, K., Zhang, G., & Wang, J. (2014). Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer. Oncology Letters, 8, 1543-1550. https://doi.org/10.3892/ol.2014.2350
MLA
Li, J., Yin, L., Su, K., Zhang, G., Wang, J."Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer". Oncology Letters 8.4 (2014): 1543-1550.
Chicago
Li, J., Yin, L., Su, K., Zhang, G., Wang, J."Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post‑operative stage Ⅱ and Ⅲ colorectal cancer". Oncology Letters 8, no. 4 (2014): 1543-1550. https://doi.org/10.3892/ol.2014.2350
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