Absence of Autophagy-related Proteins Expression is Associated with Poor Prognosis in Patients with Colorectal Adenocarcinoma

Overview

Journal Gastroenterol Res Pract

Publisher Wiley

Specialty Gastroenterology

Date 2014 Apr 12

PMID 24723943

Citations 27

Authors

Ji Hye Choi

Young-Seok Cho

Yoon Ho Ko

Soon Uk Hong

Jin Hee Park

Myung Ah Lee

Affiliations

Soon will be listed here.

Abstract

Background/Aim. Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and the progression of human cancers. The aim of this study was to investigate the expression levels of autophagy-related proteins in colorectal cancer (CRC) and to evaluate their prognostic significance. Methods. This study is a retrospective review of immunohistochemical and clinicopathological data. All specimens evaluated were obtained from 263 patients with colorectal cancer who had undergone surgery between November 1996 and August 2007. The primary outcomes measured were the expression levels of three autophagy-related proteins (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B (LC3B)) by immunohistochemistry and its association in clinicopathological parameters and patient survival. Results. The autophagy-related protein expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1, and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the expression of autophagy-related proteins was significant for all protein pairs. Multivariate analysis showed that negative LC3B expression and absence of autophagy-related proteins expression were independently associated with poor prognosis. Conclusion. Absence of autophagy-related proteins expression is associated with poor clinical outcome in CRC, suggesting that these proteins have potential uses as novel prognostic markers.

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References

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A . Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003; 112(12):1809-20. PMC: 297002. DOI: 10.1172/JCI20039. View

Yoshioka A, Miyata H, Doki Y, Yamasaki M, Sohma I, Gotoh K . LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers. Int J Oncol. 2008; 33(3):461-8. View

Pisani P, Parkin D, Bray F, Ferlay J . Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999; 83(1):18-29. DOI: 10.1002/(sici)1097-0215(19990924)83:1<18::aid-ijc5>3.0.co;2-m. View

Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y . Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Res. 2007; 67(20):9677-84. DOI: 10.1158/0008-5472.CAN-07-1462. View

Watanabe T, Wu T, Catalano P, Ueki T, Satriano R, Haller D . Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 2001; 344(16):1196-206. PMC: 3584633. DOI: 10.1056/NEJM200104193441603. View

Sivridis E, Koukourakis M, Zois C, Ledaki I, Ferguson D, Harris A . LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas. Am J Pathol. 2010; 176(5):2477-89. PMC: 2861112. DOI: 10.2353/ajpath.2010.090049. View

Mizushima N, Yoshimori T, Levine B . Methods in mammalian autophagy research. Cell. 2010; 140(3):313-26. PMC: 2852113. DOI: 10.1016/j.cell.2010.01.028. View

Dalby K, Tekedereli I, Lopez-Berestein G, Ozpolat B . Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy. 2010; 6(3):322-9. PMC: 2914492. DOI: 10.4161/auto.6.3.11625. View

Jo Y, Kim S, Park I, Park S, Jin D, Hong S . Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis. PLoS One. 2013; 7(12):e52705. PMC: 3527592. DOI: 10.1371/journal.pone.0052705. View

10.

Zheng H, Zhang X, Wang X, Sun B . Autophagy enhances the aggressiveness of human colorectal cancer cells and their ability to adapt to apoptotic stimulus. Cancer Biol Med. 2013; 9(2):105-10. PMC: 3643655. DOI: 10.3969/j.issn.2095-3941.2012.02.004. View

11.

Klionsky D . Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007; 8(11):931-7. DOI: 10.1038/nrm2245. View

12.

Wangefjord S, Manjer J, Gaber A, Nodin B, Eberhard J, Jirstrom K . Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men but not in women in a prospective, population-based cohort study. Biol Sex Differ. 2011; 2:10. PMC: 3179695. DOI: 10.1186/2042-6410-2-10. View

13.

Park J, Huang S, Wu T, Foster N, Sinicrope F . Prognostic impact of Beclin 1, p62/sequestosome 1 and LC3 protein expression in colon carcinomas from patients receiving 5-fluorouracil as adjuvant chemotherapy. Cancer Biol Ther. 2012; 14(2):100-7. PMC: 3571991. DOI: 10.4161/cbt.22954. View

14.

Ahn C, Jeong E, Lee J, Kim M, Kim S, Kim S . Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers. APMIS. 2008; 115(12):1344-9. DOI: 10.1111/j.1600-0463.2007.00858.x. View

15.

Lista P, Straface E, Brunelleschi S, Franconi F, Malorni W . On the role of autophagy in human diseases: a gender perspective. J Cell Mol Med. 2011; 15(7):1443-57. PMC: 3823190. DOI: 10.1111/j.1582-4934.2011.01293.x. View

16.

Roy S, Debnath J . Autophagy and tumorigenesis. Semin Immunopathol. 2010; 32(4):383-96. PMC: 2999728. DOI: 10.1007/s00281-010-0213-0. View

17.

Levine B, Kroemer G . Autophagy in the pathogenesis of disease. Cell. 2008; 132(1):27-42. PMC: 2696814. DOI: 10.1016/j.cell.2007.12.018. View

18.

Tschan M, Simon H . The role of autophagy in anticancer therapy: promises and uncertainties. J Intern Med. 2010; 268(5):410-8. DOI: 10.1111/j.1365-2796.2010.02266.x. View

19.

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S . Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7):844-7. DOI: 10.1038/nm0798-844. View

20.

Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y . Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009; 10(7):458-67. DOI: 10.1038/nrm2708. View