Expression and Significance of Bmi-1 and P16 in Oral Carcinogenesis.

doi:10.13701/j.cnki.kqyxyj.2016.10.012

Abstract

Abstract: Objective: To investigate the expression of Bmi-1 and P16 proteins in oral precancerous lesions and oral squamous cell carcinomas (OSCC), and elucidate their possible roles pathway in oral carcinogenesis.Methods: The tissues of 10 cases of normal oral epithelium, 31 cases of different-degree epithelium dysplasia and 61 cases of OSCC with different differentiation were collected and investigated for the expression of Bmi-1 and P16 proteins by using immunohistochemistry. The clinical and pathological significance of Bmi-1 over-expression in oral carcinogenesis was statistically analyzed by SPSS11.5.Results: The percentages of positive staining for Bmi-1 were 0 % in normal oral mucosa, 29% (9/31) in epithelial dysplasia and 62.3% (38/61) in OSCC, respectively. The percentages of positive staining for P16 were 100% (10/10) in normal oral mucosa, 77.4% (24/31) in epithelial dysplasia and 47.5% (29/61) in OSCC, respectively. The percentage of Bmi-1 over-expression with negative P16 staining in OSCC was significantly higher than that in OSCC with positive P16 staining (P<0.05), and there was a negative correlation between the expression of Bmi-1 and P16 in OSCC (r=-0.414, P<0.05). In addition, the over-expression of Bmi-1 and low-expression of P16 were positively correlated with TNM stage and lymph node metastasis in OSCC (P<0.05).Conclusion: Up-regulation of Bmi-1 was an early event in oral carcinogenesis, and might be caused by the down-regulation of P16 in OSCC, closely correlated with TNM stage and lymph node metastasis. Bmi-1 could be used as a marker for assessing the progression and prognosis of OSCC patients.

Key words: Bmi-1, P16, Precancerous lesion, Oral squamous cell carcinoma

CLC Number:

R739.8

LI Yong, WANG Chun-feng, ZHAO Guang-ye, LIU Yi-long, HUANG Yuan-qing, CAI Yang.. Expression and Significance of Bmi-1 and P16 in Oral Carcinogenesis.[J]. Journal of Oral Science Research, 2016, 32(10): 1051-1055.

References

[1] van Lohuizen M,Frasch M,Wientjens E,et al. Sequence similarity between the mammalian bmi-1 proto-oncogene and the Drosophila regulatory genes Psc and Su(z)2[J]. Nature,1991,353(6342)∶353-355
[2] Breuer Roderick HJ,Snijders Peter JF. Smit Egbert F.Increased Expression of the EZH2 Polycomb Group Gene in BMI-1-Positive Neoplastic Cells during Bronchial Carcinogenesis[J]. Neoplasia,2004,6(6)∶736-738
[3] 姚冬颖.食管鳞癌组织中Bmi-1、P16和CyclinD1的表达及临床意义[J].中国老年学杂志,2015,11(35)∶6352-6353
[4] Kamb A,Gruis NA,Weaver-Feldhaus J,et al. A cell cycle regulator potentially involved in genesis of many tumor types [J]. Science,1994,264(5157)∶436-439
[5] Itahana K,Zou Y,Itahana Y,et al. Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1 [J]. Mol Cell Biol,2003,23(1)∶389-401
[6] 胡继卫,孙志国,马杰,等.Bmi-1、P16蛋白在乳腺癌组织中的表达及相关性研究[J].实用临床医药杂志,2014,18(13)∶33-36
[7] Breuer RH,Snijders PJ,Sutedja CT,et al. Expression of the p16INK4a gene product,methylation of the p16INK4a promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions [J]. Lung Cancer,2005,48(3)∶299-306
[8] MK Kang,RH Kim,SJ Kim,et al. Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival [J]. British Journal of Cancer,2007,96(1)∶126-133
[9] Rocco JW,Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression [J]. Exp Cell Res,2001,264(1)∶42-55
[10] Bca S,Tort F,Pinyol M,et al. BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas [J]. Cancer Res,2001,61(6)∶2409-2412
[11] Vonlanthen S,Heighway J,Ahermatt HJ,et al. The Bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression [J]. Br J Cancer,2001,84(10)∶1372-1376
[12] Song LB,Zeng MS,Liao WT, et al. Bmi-1 is a novel molecularmarker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells [J]. Cancer Res,2006,66(12)∶6225-6232

[1]	GAO Antian, LIN Zitong. Advancement of Optical Imaging on Precise Assessment for Surgical Margin of Oral Squamous Cell Carcinoma [J]. Journal of Oral Science Research, 2020, 36(5): 413-415.
[2]	HU Qingang, ZHAO Xingxing. Advancement of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma [J]. Journal of Oral Science Research, 2020, 36(4): 309-313.
[3]	GUO Junfeng, ZHANG Gang, TAN Yinghui. Expression of CYP27B1 in Oral Squamous Cell Carcinoma and Its Relationship with Prognosis [J]. Journal of Oral Science Research, 2020, 36(10): 930-933.
[4]	XIE Long, SANG Lei, SONG Zhuoying, JIANG Yanjun. Diagnostic Values of Salivary MicroRNA-375 for OSCC and Its Effects on Biological Function of OSCC Cells [J]. Journal of Oral Science Research, 2019, 35(9): 883-888.
[5]	GAO Xu, ZHOU Yang, LI Chen, XUE Xiao-han, WEI Xiu-feng. Expression and Significance of Eya4 in Oral Squamous Cell Carcinoma [J]. Journal of Oral Science Research, 2019, 35(6): 555-558.
[6]	ZHOU Tong, ZHANG Tong-fei, ZHANG Ze-bing, QUAN Hai-ying. Influence of MSA on Proliferation, Migration, Apoptosis, and Cell Cycle of Oral Squamous Cell Carcinoma Tca8113 and KB Cells [J]. Journal of Oral Science Research, 2019, 35(6): 568-572.
[7]	XIONG Jing, HE Yuan-chun, LIU Jie, ZHANG Ying, LI Yong-qiang, QIU Yong-qi, ZHUANG Rui. Resveratrol Inhibits Glycolysis of Oral Squamous Cell Carcinoma by Regulating mTOR/ PKM2 Axis [J]. Journal of Oral Science Research, 2019, 35(6): 573-576.
[8]	LU Zhan-yi, HU Qin-gang, CHEN Sheng, YANG Yan, DING Liang, NI Yan-hong. Significance of TGF-β1 Expression and Clinicopathological Characteristics on Prognosis for Oral Squamous Cell Carcinoma Patients. [J]. Journal of Oral Science Research, 2019, 35(5): 433-438.
[9]	LIU Yan-ling, ZHAO Xi, YU Li, NIE Min-hai. Expression and Clinical Significance of SOX-9 in Human Oral Squamous Cell Carcinoma. [J]. Journal of Oral Science Research, 2019, 35(5): 439-442.
[10]	BAI Zhen-yu, WANG Kai, LIU De-yu, HUANG Xie-shan. Expression of LncRNA FAL1 in Oral Squamous Cell Carcinoma and Its Relationship with Prognosis [J]. Journal of Oral Science Research, 2019, 35(4): 360-363.
[11]	WANG Xiao-le, JIA Rong. Relationship between Distribution of Age and Tumor Biomarkers in Patients with Oral Squamous Cell Carcinoma [J]. Journal of Oral Science Research, 2019, 35(3): 238-241.
[12]	WU Jun-feng, SHI Bin, CAO Yu-jie, CHEN Fa, CAO Rong-kai, ZHANG Shi-lei, HUANG Yue. Influence Factor on Prognosis of the Elderly with Oral Squamous Cell Carcinoma in Fujian Area [J]. Journal of Oral Science Research, 2019, 35(3): 242-245.
[13]	WANG Yu-mei, LIU Wei-wei, CHEN Li. Expression of Serum Annexin A2 in Oral Squamous Cell Carcinoma and Its Relationship with Radiosensitivity. [J]. Journal of Oral Science Research, 2019, 35(2): 133-136.
[14]	LI Yong-wei, QIU Xun-ding, GU Ming, DENG Yi, XIE Li-li. Effect of FMNL2 Gene on Invasion, Migration, and NF-κB Signal in Oral Squamous Cell Carcinoma. [J]. Journal of Oral Science Research, 2019, 35(2): 137-141.
[15]	WANG Xiao-long, CAO Shun-shun, ZHANG Peng, SHU Chuan-ji, XIA Lin.. Expression of Homo Sapiens Longevity Assurance Homologue 2 of Yeast LAG1 in Oral Squamous Cell Carcinoma and Its Effect on Cell Proliferation and Invasion. [J]. Journal of Oral Science Research, 2019, 35(2): 142-146.