Expressions of GRP78 and GRP94 in Human Rectal Adenocarcinoma and Their Clinical Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUGu ^1,2 , ZHOUJian-ping ¹ , YANGZhu-lin ³ , LIUDong-cai ¹ , LUOYi-min ² ,  ZHANGJian-wen ²

1. Department of Geratic Surgery, The 2nd Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China;
2. Department of General Surgery, The 1 st People's Hospital of Chenzhou, Chenzhou 423000, Hunan Province, China;
3. Department of Liver Laboratory, The 2 nd Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China;

Corresponding author：

ZHANGJian-wen, Email: lj2307@163.com

Keywords：

Rectal adenocarcinoma; Glucose regulated protein 78; Glucose regulated protein 94; Immunohisto-chemistry

DOI：

10.7507/1007-9424.20150055

Video：

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Objective To explore the expressions of glucose regulated protein (GRP) 78 and GRP94 in rectal adenocarcinoma and their clinical significances. Methods In 45 paraffin-embedded sections of rectal adenocarcinoma tissues and adjacent normal tissues, the expressions of GRP78 and GRP94 were examined by EnVision^TM. Results The positive rates of GRP78 and GRP94 protein expression in the rectal adenocarcinoma tissues were 53.33% (24/45) and 53.33% (24/45), while those in the adjacent normal tissues were 13.33% (6/45) and 15.56% (7/45), respectively. There was a statistical significance of the expression of GRP78 or GRP94 between the tumor tissues and the adjacent normal tissues (all P < 0.001), and it was found that the positive expression rates were relevant to the extent of differentiation, Dukes stage, and lymph node metastasis of cancer (all P < 0.05), but not to the patient's sex, age, and size of tumor (all P > 0.05). And there was a statistical significance in Spearman method about the rate of positive expression between GRP78 and GRP94 (r_s=0.464, P < 0.01). Conclusion GRP78 and GRP94 protein is highly expressed in rectal adenocarcinoma tissue, related to its metastasis and invasion, might be used as a useful indicator to judge the malignant degree.

Citation： LIUGu, ZHOUJian-ping, YANGZhu-lin, LIUDong-cai, LUOYi-min, ZHANGJian-wen. Expressions of GRP78 and GRP94 in Human Rectal Adenocarcinoma and Their Clinical Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(2): 204-207. doi: 10.7507/1007-9424.20150055 Copy

1.	Ahn JH, Yu HK, Lee HJ, et al. Suppression of colorectal cancer liver metastasis by apolipoprotein (a) kringleⅤin a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. PLoS One, 2014, 9(4): e93794.
2.	Li W, Wang W, Li Y, et al. Proteomics analysis of normal and senescent NG108-15 cells: GRP78 plays a negative role in cisplatin-induced senescence in the NG108-15 cell line. PLoS One, 2014, 9(3): e90114.
3.	Pi LH, Li XM, Song Q, et al. Knockdown of glucose-regulated protein 78 abrogates chemoresistance of hypopharyngeal carcinoma cells to cisplatin induced by unfolded protein in response to severe hypoxia. Oncol Lett, 2014, 7(3): 685-692.
4.	田若阳, 武昕.葡萄糖调节蛋白78和钙网蛋白在外阴鳞癌中的表达及意义.中国医科大学学报, 2013, 42(8): 678-681.
5.	杨磊, 杨书云, 季建美, 等.葡萄糖调节蛋白78在胃癌组织中的表达及其临床意义.中华肿瘤杂志, 2013, 35(11): 837-842.
6.	Su R, Li Z, Song H, et al. Grp78 promotes the invasion of hepatocellular carcinoma. BMC Cancer, 2010, 19(10): 20.
7.	Duzgun A, Bedir A, Ozdemir T, et al. Effect of dexamethasone on unfolded protein response genes (MTJ1, Grp78, Grp94, CHOP, HMOX-1) in HEp2 cell line. Indian J Biochem Biophys, 2013, 50(6): 505-510.
8.	Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
9.	李宏伟, 张海, 许若飞, 等.结直肠腺癌中Galectin-3、Fascin-1和β-catenin蛋白表达与其临床病理特征的关系.中国普外基础与临床杂志, 2012, 19(4): 410-415.
10.	陈纲, 李世拥, 于波, 等.直肠癌术前放化疗反应的相关因素分析.中国普外基础与临床杂志, 2014, 21(2): 177-181.
11.	陈干农, 马勇, 杨竹林.儿童肝母细胞瘤肝组织中GRP78和GRP94表达及其临床病理意义.中国当代儿科杂志, 2010, 12(8): 634-636.
12.	颜晓丽, 高青, 李禄椿.葡萄糖调节蛋白78对胃癌SGC7901细胞侵袭和转移的影响.重庆医科大学学报, 2010, 35(9): 1332-1335.
13.	Zhu G, Wang M, Spike B, et al. Differential requirement of GRP94 and GRP78 in mammary gland development. Sci Rep, 2014, 4: 5390.
14.	Dejeans N, Glorieux C, Guenin S, et al. Overexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: Implications for tumor recurrence. Free Radic Biol Med, 2012, 52(6): 993-1002.
15.	Xing X, Li Y, Liu H, et al. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal carcinoma and regulates colorectal carcinoma cell growth and apoptosis. Acta Histochem, 2011, 113(8): 777-782.
16.	Huang TT, Chen JY, Tseng CE, et al. Decreased GRP78 protein expression is a potential prognostic marker of oral squamous cell carcinoma in Taiwan. J Formos Med Assoc, 2010, 109(5): 326-337.
17.	Takahashi H, Wang JP, Zheng HC, et al. Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis. Histol Histopathol, 2011, 26(6): 663-671.
18.	Sun Q, Hua J, Wang Q, et al. Expressions of GRP78 and Bax associate with differentiation, metastasis, and apoptosis in non-small cell lung cancer. Mol Biol Rep, 2012, 39(6): 6753-6761.
19.	Santón A, García-Cosío M, Cristóbal E, et al. Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance. Histopathology, 2011, 58(7): 1072-1080.
20.	Ma KX, Chen GW, Shi CY, et al. Molecular characterization of the glucose-regulated protein 78 (GRP78) gene in planarian Dugesia japonica. Comp Biochem Physiol B Biochem Mol Biol, 2014, 171: 12-17.
21.	Zheng HC, Takahashi H, Li XH, et al. Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol, 2008, 39(7): 1042-1049.
22.	Zhu G, Lee AS. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol, 2014 Dec 29. doi: 10.1002/jcp.24923.[Epubaheadofprint].
23.	Zhang C, Gao J, Zhang L. Effect of laminarin on the expression of GRP78 and GRP94 in rat after unilateral ureteral obstruction. Scand J Urol Nephrol, 2012, 46(4): 267-272.

1. Ahn JH, Yu HK, Lee HJ, et al. Suppression of colorectal cancer liver metastasis by apolipoprotein (a) kringleⅤin a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. PLoS One, 2014, 9(4): e93794.
2. Li W, Wang W, Li Y, et al. Proteomics analysis of normal and senescent NG108-15 cells: GRP78 plays a negative role in cisplatin-induced senescence in the NG108-15 cell line. PLoS One, 2014, 9(3): e90114.
3. Pi LH, Li XM, Song Q, et al. Knockdown of glucose-regulated protein 78 abrogates chemoresistance of hypopharyngeal carcinoma cells to cisplatin induced by unfolded protein in response to severe hypoxia. Oncol Lett, 2014, 7(3): 685-692.
4. 田若阳, 武昕.葡萄糖调节蛋白78和钙网蛋白在外阴鳞癌中的表达及意义.中国医科大学学报, 2013, 42(8): 678-681.
5. 杨磊, 杨书云, 季建美, 等.葡萄糖调节蛋白78在胃癌组织中的表达及其临床意义.中华肿瘤杂志, 2013, 35(11): 837-842.
6. Su R, Li Z, Song H, et al. Grp78 promotes the invasion of hepatocellular carcinoma. BMC Cancer, 2010, 19(10): 20.
7. Duzgun A, Bedir A, Ozdemir T, et al. Effect of dexamethasone on unfolded protein response genes (MTJ1, Grp78, Grp94, CHOP, HMOX-1) in HEp2 cell line. Indian J Biochem Biophys, 2013, 50(6): 505-510.
8. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
9. 李宏伟, 张海, 许若飞, 等.结直肠腺癌中Galectin-3、Fascin-1和β-catenin蛋白表达与其临床病理特征的关系.中国普外基础与临床杂志, 2012, 19(4): 410-415.
10. 陈纲, 李世拥, 于波, 等.直肠癌术前放化疗反应的相关因素分析.中国普外基础与临床杂志, 2014, 21(2): 177-181.
11. 陈干农, 马勇, 杨竹林.儿童肝母细胞瘤肝组织中GRP78和GRP94表达及其临床病理意义.中国当代儿科杂志, 2010, 12(8): 634-636.
12. 颜晓丽, 高青, 李禄椿.葡萄糖调节蛋白78对胃癌SGC7901细胞侵袭和转移的影响.重庆医科大学学报, 2010, 35(9): 1332-1335.
13. Zhu G, Wang M, Spike B, et al. Differential requirement of GRP94 and GRP78 in mammary gland development. Sci Rep, 2014, 4: 5390.
14. Dejeans N, Glorieux C, Guenin S, et al. Overexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: Implications for tumor recurrence. Free Radic Biol Med, 2012, 52(6): 993-1002.
15. Xing X, Li Y, Liu H, et al. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal carcinoma and regulates colorectal carcinoma cell growth and apoptosis. Acta Histochem, 2011, 113(8): 777-782.
16. Huang TT, Chen JY, Tseng CE, et al. Decreased GRP78 protein expression is a potential prognostic marker of oral squamous cell carcinoma in Taiwan. J Formos Med Assoc, 2010, 109(5): 326-337.
17. Takahashi H, Wang JP, Zheng HC, et al. Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis. Histol Histopathol, 2011, 26(6): 663-671.
18. Sun Q, Hua J, Wang Q, et al. Expressions of GRP78 and Bax associate with differentiation, metastasis, and apoptosis in non-small cell lung cancer. Mol Biol Rep, 2012, 39(6): 6753-6761.
19. Santón A, García-Cosío M, Cristóbal E, et al. Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance. Histopathology, 2011, 58(7): 1072-1080.
20. Ma KX, Chen GW, Shi CY, et al. Molecular characterization of the glucose-regulated protein 78 (GRP78) gene in planarian Dugesia japonica. Comp Biochem Physiol B Biochem Mol Biol, 2014, 171: 12-17.
21. Zheng HC, Takahashi H, Li XH, et al. Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol, 2008, 39(7): 1042-1049.
22. Zhu G, Lee AS. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol, 2014 Dec 29. doi: 10.1002/jcp.24923.[Epubaheadofprint].
23. Zhang C, Gao J, Zhang L. Effect of laminarin on the expression of GRP78 and GRP94 in rat after unilateral ureteral obstruction. Scand J Urol Nephrol, 2012, 46(4): 267-272.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of GRP78 and GRP94 in Human Rectal Adenocarcinoma and Their Clinical Significances

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