Skip to main content
SpringerLink
Log in

Prognostic Significance of Beclin-1 Expression in Laryngeal Squamous Cell Carcinoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Beclin-1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The aim of the present investigation was to analyze the Beclin-1 protein expression and to assess its prognostic significance in tissue of laryngeal squamous cell carcinoma (LSCC). Beclin-1 protein expression in 82 primary laryngeal squamous cell carcinoma and 40 paracarcinoma non-tumor tissue samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients’ outcome. The expression of Beclin-1 in tumor tissues was significantly lower than that in non-tumor tissues (P = 0.035). Reduced Beclin-1 expression was significantly correlated with lymph node metastases (P = 0.021). Kaplan–Meier survival estimates showed a significant correlation between Beclin-1 expression and patient’s survival rate (log-rank P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P = 0.048) and Beclin-1 expression (P = 0.029) were statistically significant, independent prognostic factors for LSCC. Our findings suggested that decreased Beclin-1 expression and lymph node metastases, as examined by immunohistochemistry, are both independent biomarker for poor prognosis of patients with LSCC.

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

References

  1. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP (2005) Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 114:806–816

    Article  PubMed  CAS  Google Scholar 

  2. Assunção Guimarães C, Linden R (2004) Programmed cell death. Apoptosis and alternative deathstyles. Eur J Biochem 271:1638–1650

    Article  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  4. Cosetti M, Yu GP, Schantz SP (2008) Five-year survival rates and time trends of laryngeal cancer in the US population. Arch Otolaryngol Head Neck Surg 134:370–379

    Article  PubMed  Google Scholar 

  5. Chu CT, Zhu J, Dagda R (2007) Beclin1-independent pathway of damage-induced mitophagy and autophagic stress: implications for neurodegeneration and cell death. Autophagy 3:663–666

    PubMed  CAS  Google Scholar 

  6. Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (2001) Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep 2:330–335

    Article  PubMed  CAS  Google Scholar 

  7. Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 100:15077–15082

    Article  PubMed  CAS  Google Scholar 

  8. Ahn CH, Jeong EG, Lee JW, Kim MS, Kim SH, Kim SS, Yoo NJ, Lee SH (2007) Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers. APMIS 115:1344–1349

    Article  PubMed  Google Scholar 

  9. Smeele LE, Leemans CR, Langendijk JA, Tiwari R, Slotman BJ, van Der Waal I, Snow GB (2000) Positive surgical margins in neck dissection specimens in patients with head and neck squamous cell carcinoma and the effect of radiotherapy. Head Neck 22:559–563

    Article  PubMed  CAS  Google Scholar 

  10. Thabet MH, Talaat M, Rizk AM (2000) Pitfalls in the surgical management of cancer of the larynx and hypopharynx. Otolaryngol Head Neck Surg 123:482–487

    Article  PubMed  CAS  Google Scholar 

  11. Sobin LH, Wittekind CH (2002) TNM classification of malignant tumours (UICC), 6th edn. Wiley-Liss, New York

    Google Scholar 

  12. Li BX, Li CY, Peng RQ, Wu XJ, Wang HY, Wan DS, Zhu XF, Zhang XS (2009) The expression of beclin 1 is associated with favorable prognosis in stage IIIB colon cancers. Autophagy 5:303–306

    Article  PubMed  Google Scholar 

  13. Kim HS, Lee SH, Do SI, Lim SJ, Park YK, Kim YW (2011) Clinicopathologic correlation of beclin-1 expression in pancreatic ductal adenocarcinoma. Pathol Res Pract 207:247–252

    Article  PubMed  CAS  Google Scholar 

  14. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, Chen G, Jin S, White E (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 21:1367–1381

    Article  PubMed  CAS  Google Scholar 

  15. Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477

    Article  PubMed  CAS  Google Scholar 

  16. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326–336

    Article  PubMed  CAS  Google Scholar 

  17. Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, Kalachikov S, Gilliam TC, Levine B (1999) Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 59:59–65

    Article  PubMed  CAS  Google Scholar 

  18. Mathew R, White E (2011) Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr Opin Genet Dev 21:113–119

    Article  PubMed  CAS  Google Scholar 

  19. Kenific CM, Thorburn A, Debnath J (2010) Autophagy and metastasis: another double-edged sword. Curr Opin Cell Biol 22:241–245

    Article  PubMed  CAS  Google Scholar 

  20. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 21:1621–1635

    Article  PubMed  CAS  Google Scholar 

  21. Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1994) Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 73:187–190

    Article  PubMed  CAS  Google Scholar 

  22. Shen Y, Li DD, Wang LL, Deng R, Zhu XF (2008) Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy 4:1067–1068

    PubMed  CAS  Google Scholar 

  23. Karantza-Wadsworth V, White E (2007) Role of autophagy in breast cancer. Autophagy 3:610–613

    PubMed  CAS  Google Scholar 

  24. Shi YH, Ding ZB, Zhou J, Qiu SJ, Fan J (2009) Prognostic significance of Beclin 1-dependent apoptotic activity in hepatocellular carcinoma. Autophagy 5:380–382

    Article  PubMed  CAS  Google Scholar 

  25. Cabanillas R, Rodrigo JP, Astudillo A, Domínguez F, Suárez C, Chiara MD (2007) P53 expression in squamous cell carcinomas of the supraglottic larynx and its lymph node metastases: new results for an old question. Cancer 109:1791–1798

    Article  PubMed  Google Scholar 

  26. Leibel SA, Scott CB, Mohiuddin M, Marcial VA, Coia LR, Davis LW, Fuks Z (1991) The effect of local-regional control on distant metastatic dissemination in carcinoma of the head and neck: results of an analysis from the RTOG head and neck database. Int J Radiat Oncol Biol Phys 21:549–556

    Article  PubMed  CAS  Google Scholar 

  27. Wan XB, Fan XJ, Chen MY, Xiang J, Huang PY, Guo L et al (2010) Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma. Autophagy 6:395–404

    Article  PubMed  CAS  Google Scholar 

  28. Koukourakis MI, Giatromanolaki A, Sivridis E, Pitiakoudis M, Gatter KC, Harris AL (2010) Beclin 1 over-and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia. Br J Cancer 103:1209–1214

    Article  PubMed  CAS  Google Scholar 

  29. Huang X, Bai HM, Chen L, Li B, Lu YC (2010) Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors. J Clin Neurosci 17:1515–1519

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr Ting Zhang for collecting patients’ survival data. We thank Daiqiang Li and Songqing Fan (Department of Pathology, Second Xiangya Hospital, Central South University) and Yunjun Deng (Central Laboratory of Medical Research, Second Xiangya Hospital, Central South University) for their evaluation of these clinical samples.

The authors have no funding, financial relationships, or conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, 37, Guoxue Lane, Chengdu, 610041, China

    Li Huang

  2. Department of Otolaryngology-Head and Neck Surgery, The Second XiangYa Hospital, Central South University, Changsha, Hunan, 410011, China

    Shuang Wang, Shi-Sheng Li & Xin-Ming Yang

Authors
  1. Li Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shi-Sheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin-Ming Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xin-Ming Yang.

Additional information

Dr Xinming Yang takes responsibility for the integrity of the content of the paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, L., Wang, S., Li, SS. et al. Prognostic Significance of Beclin-1 Expression in Laryngeal Squamous Cell Carcinoma. Pathol. Oncol. Res. 19, 771–777 (2013). https://doi.org/10.1007/s12253-013-9642-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-013-9642-0

Keywords

Search

Navigation