Skip to main content

Advertisement

SpringerLink
Log in

Overexpression of Autophagy-Related 16-Like 1 in Patients with Oral Squamous Cell Carcinoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Dyregulation of autophagy has been reported in various human cancers including oral squamous cell carcinoma (OSCC). The objective of this study was to link expression of autophagy-related 16-like 1 (ATG16L1), a protein essential for autophagosome formation, to clinical outcome in a cohort of 90 OSCC patients. Expression level of ATG16L1 was assessed by immunohistochemistry and an immunoreactivity score (IRS), ranging from 0 to 9, was assigned to each case. The results were correlated with clinicopathological parameters and outcome of patients. Twenty-seven patients (30 %) exhibited ATG16L1 overexpression as indicated by an IRS of 9. Overexpression of ATG16L1 was significantly associated with disease stage (p = 0.001), size (p = 0.031) of the tumor, lymph node metastasis (p = 0.004), and histological grade (p = 0.038). ATG16L1 overexpression significantly affected the overall survival (p = 0.020) and time to recurrence (p = 0.031) of OSCC patients in Kaplan-Meier analysis. The present study suggested that ATG16L1 may be used as a biomarker for selecting OSCC patients with a more aggressive phenotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

OSCC:

Oral squamous cell carcinoma

ATG16L1:

Autophagy-related 16-like 1

IRS:

Immunoreactivity score

ROC:

Receiver operating characteristics

OS:

Overall survival

TTR:

Time to recurrence

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  2. Ranadive KJ, Ranadive SN, Shivapurkar NM, Gothoskar SV (1979) Betel quid chewing and oral cancer: experimental studies on hamsters. International Journal of Cancer Journal International du Cancer 24(6):835–843

    Article  CAS  PubMed  Google Scholar 

  3. Mashberg A, Boffetta P, Winkelman R, Garfinkel L (1993) Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans. Cancer 72(4):1369–1375

    Article  CAS  PubMed  Google Scholar 

  4. Pindborg JJ, Reibel J, Roed-Peterson B, Mehta FS (1980) Tobacco-induced changes in oral leukoplakic epithelium. Cancer 45(9):2330–2336

    Article  CAS  PubMed  Google Scholar 

  5. Paterson IC, Eveson JW, Prime SS (1996) Molecular changes in oral cancer may reflect aetiology and ethnic origin. Eur J Cancer B Oral Oncol 32B(3):150–153

    Article  CAS  PubMed  Google Scholar 

  6. Park JY, Muscat JE, Ren Q, Schantz SP, Harwick RD, Stern JC, Pike V, Richie JP Jr, Lazarus P (1997) CYP1A1 and GSTM1 polymorphisms and oral cancer risk. Cancer Epidemiol Biomarkers Prev: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 6(10):791–797

    CAS  Google Scholar 

  7. Elwood JM, Pearson JC, Skippen DH, Jackson SM (1984) Alcohol, smoking, social and occupational factors in the aetiology of cancer of the oral cavity, pharynx and larynx. International Journal of Cancer Journal International du Cancer 34(5):603–612

    Article  CAS  PubMed  Google Scholar 

  8. Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290(5497):1717–1721

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Mizushima N (2007) Autophagy: process and function. Genes Dev 21(22):2861–2873. doi:10.1101/gad.1599207

    Article  CAS  PubMed  Google Scholar 

  10. Mathew R, Karantza-Wadsworth V, White E (2007) Role of autophagy in cancer. Nat Rev Cancer 7(12):961–967. doi:10.1038/nrc2254

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Mizushima N, Noda T, Ohsumi Y (1999) Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J 18(14):3888–3896. doi:10.1093/emboj/18.14.3888

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Nomura H, Uzawa K, Yamano Y, Fushimi K, Ishigami T, Kouzu Y, Koike H, Siiba M, Bukawa H, Yokoe H, Kubosawa H, Tanzawa H (2009) Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis. Hum Pathol 40(1):83–91. doi:10.1016/j.humpath.2008.06.018

    Article  CAS  PubMed  Google Scholar 

  13. Hippert MM, O’Toole PS, Thorburn A (2006) Autophagy in cancer: good, bad, or both? Cancer Res 66(19):9349–9351. doi:10.1158/0008-5472.CAN-06-1597

    Article  CAS  PubMed  Google Scholar 

  14. Kimmelman AC (2011) The dynamic nature of autophagy in cancer. Genes Dev 25(19):1999–2010. doi:10.1101/gad.17558811

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Tang JY, Hsi E, Huang YC, Hsu NC, Chu PY, Chai CY (2013) High LC3 expression correlates with poor survival in patients with oral squamous cell carcinoma. Hum Pathol 44(11):2558–2562. doi:10.1016/j.humpath.2013.06.017

    Article  CAS  PubMed  Google Scholar 

  16. Wu WK, Coffelt SB, Cho CH, Wang XJ, Lee CW, Chan FK, Yu J, Sung JJ (2012) The autophagic paradox in cancer therapy. Oncogene 31(8):939–953. doi:10.1038/onc.2011.295

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of Interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jen-Yang Tang

  2. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jen-Yang Tang

  3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Edward Hsi & Nicholas Chung-Heng Hsu

  4. Department of Pathology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan

    Ya-Chun Huang & Chee-Yin Chai

  5. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Wen-Chi Yang

  6. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsueh-Wei Chang

  7. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    Chee-Yin Chai

  8. Department of Pathology, St. Martin De Porres Hospital, No. 565, Sec. 2, Daya Road, Chiayi, Taiwan

    Pei-Yi Chu

  9. School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

    Pei-Yi Chu

Authors
  1. Jen-Yang Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edward Hsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Chun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas Chung-Heng Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen-Chi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hsueh-Wei Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chee-Yin Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pei-Yi Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chee-Yin Chai or Pei-Yi Chu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, JY., Hsi, E., Huang, YC. et al. Overexpression of Autophagy-Related 16-Like 1 in Patients with Oral Squamous Cell Carcinoma. Pathol. Oncol. Res. 21, 301–305 (2015). https://doi.org/10.1007/s12253-014-9821-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-014-9821-7

Keywords

Search

Navigation