三阴型乳腺癌中S1PR1、S1PR4的表达及其临床意义
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摘要
目的探讨1-磷酸神经鞘氨醇受体1(sphingosine-1 phosphate receptor 1,S1PR1)和1-磷酸神经鞘氨醇受体4(sphingosine-1 phosphate receptor 4,S1PR4)在三阴型乳腺癌(triple-negative breast carcinoma,TNBC)中的表达,分析两者与TNBC临床病理特征的关系。方法采用免疫组化SP法和图像分析软件检测72例TNBC中S1PR1、S1PR4和CD68的表达,分析S1PR1、S1PR4与TNBC临床病理特征的相关性。结果 S1PR1高、中、低表达组的Ki-67增殖指数分别为48.89%、36.11%和26.48%,三组差异有统计学意义(P<0.001)。S1PR4高、中、低表达组的Ki-67增殖指数分别为42.83%、31.43%和28.93%,三组差异有统计学意义(P=0.007)。S1PR1高、中、低表达组的淋巴结转移率分别为31.4%、48.6%和20.0%,差异有统计学意义(P=0.012)。S1PR4高、中、低表达组的淋巴结转移率分别为54.3%、40.0%和5.7%,差异有统计学意义(P=0.010)。S1PR1高、中和低表达组的CD68阳性率分别为47.22%、42.59%和31.48%,差异有统计学意义(P=0.036)。不同S1PR1表达组间和不同S1PR4表达组间的TNBC生存率差异均无统计学意义(P=0.209,P=0.593)。结论 S1PR1、S1PR4高表达的TNBC具有高增殖活性和淋巴结转移率,且肿瘤间质巨噬细胞数量增加,S1PR1、S1PR4表达与TNBC的生存无关。
Purpose To investigate the expression of sphingosine-1 phosphate receptor 1( S1PR1) and sphingosine-1phosphate receptor 4( S1PR4) in triple negative breast carcinoma( TNBC) and to evaluate its correlation with the clinicopathologic features of TNBC. Methods 72 cases of tissue slides of TNBC were stained immunohistochemically and analyzed with image processing to calculate the S1 PR1 and S1 PR4 expression.Correlations of the S1PR1 and S1PR4 expression with the clinicopathologic features of TNBC were studied. Results Ki-67 index of high,moderate and low expression of the S1PR1 in TNBC were 48. 89%,36. 11% and 26. 48%,respectively. The difference among them was significance( P < 0. 001). Ki-67 index of high,moderate and low expression of the S1PR4 in TNBC were42. 83%,31. 43% and 28. 93%,respectively. The difference among them was significance( P = 0. 007). The positive rate of lymph node of high,moderate and low expression of the S1 PR1 in TNBC were 31. 4%,48. 6% and 20. 0%,respectively. The difference among them was significance( P = 0. 012). The positive rate of lymph node of high,moderate and low expression of the S1 PR4 in TNBC were 54. 3%,40. 0% and 5. 7%,respectively. The difference among them was significance( P =0. 010). The CD68 positive rate of high,moderate and low expression of the S1 PR1 in TNBC were 47. 22%,42. 59% and31. 48%,respectively. The difference among them was significance( P = 0. 036). Both the difference of survive rate among high,moderate and low expression of the S1PR1 and S1PR4 were not significance( P = 0. 209 and P = 0. 593). Conclusion High expression of S1PR1 and S1PR4 may contribute to the cellular proliferation and lymph node metastases in TNBC. The survive rate of TNBC maybe not related with both the S1PR1 and S1 PR4 expression.
Purpose To investigate the expression of sphingosine-1 phosphate receptor 1( S1PR1) and sphingosine-1phosphate receptor 4( S1PR4) in triple negative breast carcinoma( TNBC) and to evaluate its correlation with the clinicopathologic features of TNBC. Methods 72 cases of tissue slides of TNBC were stained immunohistochemically and analyzed with image processing to calculate the S1 PR1 and S1 PR4 expression.Correlations of the S1PR1 and S1PR4 expression with the clinicopathologic features of TNBC were studied. Results Ki-67 index of high,moderate and low expression of the S1PR1 in TNBC were 48. 89%,36. 11% and 26. 48%,respectively. The difference among them was significance( P < 0. 001). Ki-67 index of high,moderate and low expression of the S1PR4 in TNBC were42. 83%,31. 43% and 28. 93%,respectively. The difference among them was significance( P = 0. 007). The positive rate of lymph node of high,moderate and low expression of the S1 PR1 in TNBC were 31. 4%,48. 6% and 20. 0%,respectively. The difference among them was significance( P = 0. 012). The positive rate of lymph node of high,moderate and low expression of the S1 PR4 in TNBC were 54. 3%,40. 0% and 5. 7%,respectively. The difference among them was significance( P =0. 010). The CD68 positive rate of high,moderate and low expression of the S1 PR1 in TNBC were 47. 22%,42. 59% and31. 48%,respectively. The difference among them was significance( P = 0. 036). Both the difference of survive rate among high,moderate and low expression of the S1PR1 and S1PR4 were not significance( P = 0. 209 and P = 0. 593). Conclusion High expression of S1PR1 and S1PR4 may contribute to the cellular proliferation and lymph node metastases in TNBC. The survive rate of TNBC maybe not related with both the S1PR1 and S1 PR4 expression.
引文
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[14]吕倩,尹水平,王弦,等.CD68和CD206阳性巨噬细胞在乳腺癌组织中的浸润及对预后影响[J].临床与实验病理学杂志,2016,32(3):252-257.
[15]朱敬凤,吴正升,聂静,等.乳腺癌中肿瘤相关巨噬细胞与CXCR4表达的关系及意义[J].临床与实验病理学杂志,2014,30(5):478-482.
[16]Nagahashi M,Ramachandran S,Kim E Y,et al.Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis[J].Cancer Res,2012,72(3):726-735.
[17]Tsuchida J,Nagahashi M,Nakajima M,et al.Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis[J].J Surg Res,2016,205(1):85-94.
[18]Xiao H Y,Watterson S H,Langevine C M,et al.Identification of tricyclic agonists of sphingosine-1-phosphate receptor 1(S1P1)employing ligand-based drug design[J].J Med Chem,2016,59(21):9837-9854.
[19]Xie Z,Liu H,Geng M.Targeting sphingosine-1-phosphate signaling for cancer therapy[J].Sci China Life Sci,2017,60(6):585-600.
[2]Patmanathan S N,Wang W,Yap L F,et al.Mechanisms of sphingosine 1-phosphate receptor signalling in cancer[J].Cell Signal,2017,34(6):66-75.
[3]Pyne N J,Mc Naughton M,Boomkamp S,et al.Role of sphingosine 1-phosphate receptors,sphingosine kinases and sphingosine in cancer and inflammation[J].Adv Biol Regul,2016,60(1):151-159.
[4]Watson C,Long J S,Orange C.High expression of sphingosine 1-phosphate receptors,S1P1 and S1P3,sphingosine kinase 1,and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients[J].Am J Pathol,2010,177(5):2205-2215.
[5]Salgado R,Denkert C,Demaria S,et al.The evaluation of tumorinfiltrating lymphocytes(TILs)in breast cancer:recommendations by an International TILs Working Group 2014[J].Ann Oncol,2015,26(2):259-271.
[6]郑唯强.乳腺癌分子病理诊断的机遇与挑战[J].临床与实验病理学杂志,2017,33(5):473-476.
[7]Maiti A,Takabe K,Hait N C.Metastatic triple-negative breast cancer is dependent on Sph Ks/S1P signaling for growth and survival[J].Cell Signal,2017,32(4):85-92.
[8]Datta A,Loo S Y,Huang B,et al.SPHK1 regulates proliferation and survival responses in triple-negative breast cancer[J].Oncotarget,2014,5(15):5920-5933.
[9]Ohotski J,Rosen H,Bittman R,et al.Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth:the role of sphingosine 1-phosphate receptor-4[J].Cell Signal,2014,26(5):1040-1047.
[10]Long J S,Edwards J,Watson C,et al.Sphingosine kinase 1 induces tolerance to human epidermal growth factor receptor 2 and prevents formation of a migratory phenotype in response to sphingosine 1-phosphate in estrogen receptor-positive breast cancer cells[J].Mol Cell Biol,2010,30(15):3827-3841.
[11]Zeng Y E,Yao X H,Yan Z P,et al.Potential signaling pathway involved in sphingosine-1-phosphate-induced epithelial-mesenchymal transition in cancer[J].Oncol Lett,2016,12(1):379-382.
[12]Tamashiro P M,Furuya H,Shimizu Y,et al.Sphingosine kinase1 mediates head&neck squamous cell carcinoma invasion through sphingosine 1-phosphate receptor 1[J].Cancer Cell Int,2014,14(1):76.
[13]Müller J,von Bernstorff W,Heidecke C D,et al.Differential S1Preceptor profiles on M1-and M2-polarized macrophages affect macrophage cytokine production and migration[J].Biomed Res Int,2017,2017(3):7584621.
[14]吕倩,尹水平,王弦,等.CD68和CD206阳性巨噬细胞在乳腺癌组织中的浸润及对预后影响[J].临床与实验病理学杂志,2016,32(3):252-257.
[15]朱敬凤,吴正升,聂静,等.乳腺癌中肿瘤相关巨噬细胞与CXCR4表达的关系及意义[J].临床与实验病理学杂志,2014,30(5):478-482.
[16]Nagahashi M,Ramachandran S,Kim E Y,et al.Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis[J].Cancer Res,2012,72(3):726-735.
[17]Tsuchida J,Nagahashi M,Nakajima M,et al.Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis[J].J Surg Res,2016,205(1):85-94.
[18]Xiao H Y,Watterson S H,Langevine C M,et al.Identification of tricyclic agonists of sphingosine-1-phosphate receptor 1(S1P1)employing ligand-based drug design[J].J Med Chem,2016,59(21):9837-9854.
[19]Xie Z,Liu H,Geng M.Targeting sphingosine-1-phosphate signaling for cancer therapy[J].Sci China Life Sci,2017,60(6):585-600.