Clinical importance of microtubule-associated protein 1 light chain 3 and mammalian target of rapamycin expression in oral leukoplakia and oral squamous cell carcinoma

doi:10.7518/hxkq.2018.06.006

Abstract

Abstract:

Objective This study aimed to investigate the expression and relationship of microtubule-associated protein 1 light chain 3 (LC3) and mammalian target of rapamycin (mTOR) in normal oral mucosa, oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC). This work also analyzed the relationship between expression levels and clinical factors. This study evaluated the clinical value of LC3B and mTOR as indices to determine the carcinogenic potential of OLK.Methods Immunohistochemistry was used to detect the expression of LC3B and mTOR in 20 cases of normal oral mucosa, 120 cases of OLK, and 30 cases of OSCC. The clinical data of 120 patients with OLK were analyzed. The relationships between expression levels and clinical factors were investigated.Results In normal oral mucosa, OLK and OSCC, the positive rates of LC3B expression were 85.0%, 65.8% and 33.3% (P<0.05), whereas the positive rates of mTOR expression were 20.0%, 48.3% and 76.7% (P<0.05). The expression levels of LC3B and mTOR were correlated and related to clinical typing of OLK (P<0.05).Conclusion LC3B and mTOR can be used as molecular biomarkers for early detection of OLK.

Key words: microtubule-associated protein 1 light chain 3, mammalian target of rapamycin, leukoplakia

CLC Number:

Xiaolin Dong,Zhiwen Liu. Clinical importance of microtubule-associated protein 1 light chain 3 and mammalian target of rapamycin expression in oral leukoplakia and oral squamous cell carcinoma[J]. West China Journal of Stomatology, 2018, 36(6): 613-618.

Figures/Tables 4

Fig.1

Tab 1

Fig.2

Tab 2

References 24

[1]	Amaravadi RK, Lippincott-Schwartz J, Yin XM , et al. Prin-ciples and current strategies for targeting autophagy for can-cer treatment[J]. Clin Cancer Res, 2011,17(4):654-666. doi: 10.1158/1078-0432.CCR-10-2634 URL pmid: 21325294
[2]	Lai K, Killingsworth M, Yong J , et al. Specific localization of LC3B in autophagosome: a correlative labelling study with nanoparticle in oral squamous cell carcinoma[J]. Exp Mol Pathol, 2017,102(3):422-427. doi: 10.1016/j.yexmp.2017.05.007 URL pmid: 28506764
[3]	Ladoire S, Penault-Llorca F, Senovilla L , et al. Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer[J]. Autophagy, 2015,11(10):1878-1890. doi: 10.1080/15548627.2015.1082022 URL pmid: 26506894
[4]	Warnakulasuriya S . Global epidemiology of oral and oro-pharyngeal cancer[J]. Oral Oncol, 2009,45(4/5):309-316. doi: 10.1016/j.oraloncology.2008.06.002 URL pmid: 18804401
[5]	Parkin DM, Läärä E, Muir CS . Estimates of the worldwide frequency of sixteen major cancers in 1980[J]. Int J Cancer, 1988,41(2):184-197. doi: 10.1002/(ISSN)1097-0215 URL
[6]	Liu W, Wang YF, Zhou HW , et al. Malignant transforma-tion of oral leukoplakia: a retrospective cohort study of 218 Chinese patients[J]. BMC Cancer, 2010,10:685. doi: 10.1186/1471-2407-10-685 URL pmid: 3009685
[7]	Jia YL, Xu M, Dou CW , et al. P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy[J]. Cell Death Dis, 2016,7(10):e2400. doi: 10.1038/cddis.2016.247 URL pmid: 27711074
[8]	Altman BJ, Jacobs SR, Mason EF , et al. Autophagy is essen-tial to suppress cell stress and to allow BCR-Abl-mediated leukemogenesis[J]. Oncogene, 2011,30(16):1855-1867. doi: 10.1038/onc.2010.561 URL pmid: 21151168
[9]	Wei H, Wei S, Gan B , et al. Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis[J]. Genes Dev, 2011,25(14):1510-1527. doi: 10.4161/auto.8.1.18171 URL pmid: 21764854
[10]	Chen HY, White E . Role of autophagy in cancer prevention[J]. Cancer Prev Res(Phila), 2011,4(7):973-983. doi: 10.1158/1940-6207.CAPR-10-0387 URL pmid: 3136921
[11]	Mathew R, Karp CM, Beaudoin B , et al. Autophagy sup-presses tumorigenesis through elimination of p62[J]. Cell, 2009,137(6):1062-1075. doi: 10.1016/j.cell.2009.03.048 URL pmid: 2802318
[12]	Kubisch J, Türei D, Földvári-Nagy L , et al. Complex regu-lation of autophagy in cancer-integrated approaches to discover the networks that hold a double-edged sword[J]. Semin Cancer Biol, 2013,23(4):252-261. doi: 10.1016/j.semcancer.2013.06.009 URL pmid: 23810837
[13]	Li Q, Gu C, Zhu Y , et al. Polymorphisms in the m TOR gene and risk of sporadic prostate cancer in an Eastern Chinese population[J]. PLoS One, 2013,8(8):e71968. doi: 10.1371/journal.pone.0071968 URL pmid: 3882253
[14]	Roy B, Pattanaik AK, Das J , et al. Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced auto-phagy in HeLa cells[J]. Chem Biol Interact, 2014,210:96-102. doi: 10.1016/j.cbi.2014.01.003 URL pmid: 24434245
[15]	Zhu W, Pan X, Li F , et al. Expression of Beclin 1 and LC3 in FIGO stage Ⅰ-Ⅱ cervical squamous cell carcinoma and relationship to survival[J]. Tumour Biol, 2012,33(5):1653-1659. doi: 10.1007/s13277-012-0421-4 URL pmid: 22648564
[16]	Jiang ZF, Shao LJ, Wang WM , et al. Decreased expression of Beclin-1 and LC3 in human lung cancer[J]. Mol Biol Rep, 2012,39(1):259-267. doi: 10.1007/s11033-011-0734-1 URL pmid: 21556768
[17]	Liu JL, Chen FF, Lung J , et al. Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma[J]. Br J Cancer, 2014,111(5):944-954. doi: 10.1038/bjc.2014.355 URL pmid: 24983366
[18]	Wu DH, Wang TT, Ruan DY , et al. Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma[J]. Biomed Pharmacother, 2018,97:195-202. doi: 10.1016/j.biopha.2017.10.025 URL
[19]	Zou Y, Ge M, Wang X . Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo[J]. Biochem Biophys Res Commun, 2017,490(2):385-392. doi: 10.1016/j.bbrc.2017.06.052 URL pmid: 28623128
[20]	Molinolo AA, Hewitt SM, Amornphimoltham P , et al. Dis-secting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative[J]. Clin Cancer Res, 2007,13(17):4964-4973. doi: 10.1158/1078-0432.CCR-07-1041 URL pmid: 17785546
[21]	Liu Y, Hidayat S, Su WH , et al. Expression and activity of mTOR and its substrates in different cell cycle phases and in oral squamous cell carcinomas of different malignant grade[J]. Cell Biochem Funct, 2007,25(1):45-53. doi: 10.1002/cbf.1332 URL pmid: 16927414
[22]	时艳辉 . 自噬相关基因mTOR和MAP1LC3B与乳腺癌发生发展关系的研究[D]. 济南: 山东师范大学, 2017.
	Shi YH . Study on relationship between mTOR and MAP1-LC3B and the development of breast cancer[D]. Jinan: Shan-dong Normal University, 2017.
[23]	张晶, 舒丽莎, 陈江平 , 等. Beclin1、MAP1LC3B和mTOR在宫颈病变中的表达及临床意义[J]. 河北北方学院学报(自然科学版), 2017,33(6):1-5.
	Zhang J, Shu LS, Chen JP , et al. Expression of Beclin1, MAP1LC3B and mTOR and their clinical significance in cervical lesions[J]. J Hebei North Univ (Nat Sci Ed), 2017,33(6):1-5.
[24]	吴淑华, 胡金龙, 何双 , 等. 大肠癌中Beclin1、LC3和mTOR的表达及意义[J]. 临床实验与病理学杂志, 2014,30(12):1333-1338. doi: 10.13315/j.cnki.cjcep.2014.12.002 URL
	Wu SH, Hu JL, He S , et al. Expression of Beclin1, LC3 and mTOR and their significance in colorectal carcinoma[J]. J Clin Exp Pathol, 2014,30(12):1333-1338. doi: 10.13315/j.cnki.cjcep.2014.12.002 URL

组织类型			n	LC3B+/%	χ²值	P值	mTOR+/%	χ²值	P值
正常口腔黏膜			20	17/85.0	15.752	0.000^#,1	4/20.0	15.867	0.000^#,1
OLK	单纯增生		30	25/83.3	5.446	0.020^*	11/36.7	2.180	0.140^**
	异常增生		90	54/60.0			47/52.2
		轻度异常	30	22/73.3	3.611	0.164^Δ	12/40.0	3.295	0.192^Δ
		中度异常	30	17/56.7			16/53.3
		重度异常	30	15/50.0			19/63.3
	合计		120	79/65.8		0.087²	58/48.3		0.018²
OSCC			30	10/33.3		0.001³	23/76.7		0.005³