Objective: To explore the expression of glucose-regulated protein 78 (GRP78) and gene associated with retinoid and interferon-induced mortality 1 (GRIM-1) in prostate cancer tissues and its clinical value for prognositic. Methods: The expression of GRP78 and GRIM-1 in eighty prostate cancer tissues and fifty benign prostatic hyperplasia tissues were performed with immunohistochemical staining, the relationship between GRP78, GRIM-1 and prostate cancer patients clinical data were compared,the over-all survival of patients were analyzed by Kaplan-Meier method, the risk factors influencingthe prognosis of prostate cancer patients were analyzed by Cox proportional hazards model. Results: The positive rate of GRIM-1 protein in the prostate cancer group (90.0%, 45/50) was significantly lower than that in the benign prostatic hyperplasia group (67.5%, 54/80) (χ2=8.578,P=0.003). The positive rate of GRP78 protein in the prostate cancer group (95.0%, 76/80) was significantly higher than that in the benign prostatic hyperplasia group (76.0%, 38/50) (χ2=10.292,P=0.001). The positive rate of GRIM-1 protein in the 2~7 score group (82.4%, 28/34) was significantly higher than in that in the 8~10 score group (56.5%, 26/46), while GRP78 positive rate in the 2~7 score group (88.2%, 30/34) was significantly higher than in the 8~10 score group (100.0%, 46/46), the difference was statistically significant (P<0.05). There was a negative correlation between GRIM-1 and GRP78 in the prostate cancer tissues (r=-0.571, P<0.001). The over-all survival in the GRIM-1 higher expression group was markedly higher than that in the lower expression group, and the over-all survival in the higher GRP78 expression group was markedly lower than that in the lower expression group, the difference was statistically significant (P<0.05). Multivariate analysis showed that Gleason score, TNM stage, pathological grade, lymph node metastasis, GRP78 and GRIM-1 expression were independent risk factors for the poor prognostic of prostate cancer (all P < 0.05). Conclusion: Aberrant expression of GRP78 and GRIM-1 in prostate cancer tissues, the up-regulated of GRP78 and down-regulated of GRIM-1 are risk factors for the poor prognostic of prostate cancer. |
[1] RICK F G,SCHALLY A V,SZALONTAY L,et al.Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases[J].Proc Natl Acad Sci U S A,2012,109(5):1655-1660.
[2] HERBERT C,LIU M,TYLDESLEY S,et al.Biochemical control with radiotherapy improves overall survival in intermediate and high-risk prostate cancer patients who have an estimated 10-year overall survival of >90%[J].Int J Radiat Oncol Biol Phys,2012,83(1):22-27.
[3] 叶定伟,朱耀.中国前列腺癌的流行病学概述和启示[J].中华外科杂志,2015,53(4):249-252.
[4] WU H M,JIANG Z F,FAN X Y,et al.Reversed expression of GRIM-1 and GRP78 in human non-small cell lung cancer[J].Hum Pathol,2014,45(9):1936-1943.
[5] HOFMANN E R,NALLAR SC,LIN L,et al.Identification and characterization of GRIM-1,a cell-death-associated gene product[J].J Cell Sci,2010,123(16):2781-2791.
[6] 吉天舒,王丹.葡萄糖调节蛋白78在肿瘤中的研究进展[J].实用肿瘤学杂志,2013,27(1):85-87.
[7] 韩丽媛,毛冬梅,辛玲,等.膜联蛋白A2和葡萄糖调节蛋白78表达与前列腺癌的关系[J].生殖医学杂志,2012,21(3):257-263.
[8] KITAGAWA Y,UENO S,IZUMI K,et al.Cumulative probability of prostate cancer detection in biopsy according to free/total PSA ratio in men with total PSA levels of 2.1-10.0 ng/ml at population screening[J].J Cancer Res Clin Oncol,2014,140(1):53-59.
[9] NALLAR S C,KALAKONDA S,LINDNER D J,et al.Tumor-derived mutations in the gene associated with retinoid interferon-induced mortality (GRIM-19) disrupt its anti-signal transducer and activator of transcription 3(STAT3) activity and promote oncogenesis[J].J Biol Chem,2013,288(11):7930-7941.
[10] MAGURUDENIYA H D,SISTA P,WESTBROOK J K,et al.Nickel(ii) α-diimine catalyst for grignard metathesis (GRIM) polymerization[J].Macromol Rapid Commun,2011,32(21):1748-1752.
[11] NALLAR S C,LIN L,SRIVASTAVA V,et al.GRIM-1,a novel growth suppressor,inhibits rRNA maturation by suppressing small nucleolar RNAs[J].PLoS One,2011,6(9):e24082.
[12] 邵玉佩,程晓东,万小云,等.卵巢上皮性癌组织中GRIM-19蛋白的表达及其临床意义[J].中华妇产科杂志,2012,47(10):751-755.
[13] TSAI H Y,YANG Y F,WU A T,et al.Endoplasmic reticulum ribosome-binding protein 1(RRBP1)overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78[J].Oncogene,2013,32(41):4921-4931.
[14] CHIU S C,HUANG S Y,CHEN S P,et al.Tanshinone ⅡA inhibits human prostate cancer cells growth by induction of endoplasmic reticulum stress in vitro and in vivo[J].Prostate Cancer Prostatic Dis,2013,16(4):315-322.
[15] 魏华,景红,吴江,等.胃癌中葡萄糖调节蛋白78和葡萄糖调节蛋白94表达的临床意义及与预后的相关性[J].首都医科大学学报,2014,(4):501-506.
[16] 付政祺,镇鸿燕,刘丽江,等.GRP78在胃癌生长中的作用[J].中国病理生理杂志,2014,12(4):625-628.
[17] AVILA M F,TORRENTE D,CABEZAS R,et al.Structural insights from GRP78-NF-κB binding interactions:A computational approach to understand a possible neuroprotective pathway in brain injuries[J].J Theor Biol,2014,345(2):43-51. |