CRT、CD47在胃癌组织中的表达及意义
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摘要
目的探讨钙网蛋白(CRT)、CD47在胃癌组织中的表达水平与临床病理参数的关系及其在胃癌组织中的意义。方法收集50例株洲市中心医院行胃癌根治术患者的病理标本及临床资料,同时收集相对应的癌旁正常组织病理标本作为对照。采用免疫组织化学法检测CRT、CD47的表达,分析两者在胃癌组织与癌旁组织中表达差异及两者与年龄、性别、肿瘤大小、淋巴结转移、肿瘤分化程度、肿瘤侵犯深度(T分期)的关系,用Kaplan-Meier绘制两者不同表达下胃癌根治术后3年总生存率曲线。结果胃癌组织中CRT、CD47阳性高表达率分别为68.0%和56.0%,显著高于癌旁组织,差异有统计学意义(P值分别为0.001和0.005)。CRT、CD47表达水平与胃癌分化程度、淋巴结转移、肿瘤侵犯深度正相关;CRT、CD47高表达组较低表达组生存时间短,差异有统计学意义(P<0.05)。结论 CRT、CD47是胃癌有潜在价值的标志物,可能为胃癌的早期诊断与免疫治疗提供潜在靶点。
Objective To investigate the expression levels of calcium net protein(CRT) and CD47 in gastric cancer tissues and its relationship with clinical parameters, to explore the significance of CRT and CD47 in gastric cancer tissues. Methods We collected the pathological specimens and clinical data of 50 patients undergoing radical gastrectomy in our hospital. At the same time, the corresponding normal tissues were collected as control group. Immunohistochemical method was used to detect the expression of CRT and CD47. We analyzed the difference of CRT and CD47 expression between gastric cancer and paracancerous tissues and their relationship with age, sex, tumor size, lymph node metastasis, tumor differentiation and tumor invasion depth(T stage). Kaplan-Meier curve was used to analyze the 3-year overall survival rate after radical resection of gastric cancer. Results The expression rates of CRT and CD47 in gastric cancer tissues were 68.0% and 56.0% respectively, significantly higher than those in adjacent normal tissues. The expression levels of CRT and CD47 were related to the differentiation degree, lymph node metastasis and tumor invasion. The survival time of high CRT and CD47 expression group was shorter than that in low expression group(P<0.05). Conclusion CRT and CD47 are potential markers of gastric cancer, which may provide potential targets for the early diagnosis and immunotherapy of gastric cancer.
Objective To investigate the expression levels of calcium net protein(CRT) and CD47 in gastric cancer tissues and its relationship with clinical parameters, to explore the significance of CRT and CD47 in gastric cancer tissues. Methods We collected the pathological specimens and clinical data of 50 patients undergoing radical gastrectomy in our hospital. At the same time, the corresponding normal tissues were collected as control group. Immunohistochemical method was used to detect the expression of CRT and CD47. We analyzed the difference of CRT and CD47 expression between gastric cancer and paracancerous tissues and their relationship with age, sex, tumor size, lymph node metastasis, tumor differentiation and tumor invasion depth(T stage). Kaplan-Meier curve was used to analyze the 3-year overall survival rate after radical resection of gastric cancer. Results The expression rates of CRT and CD47 in gastric cancer tissues were 68.0% and 56.0% respectively, significantly higher than those in adjacent normal tissues. The expression levels of CRT and CD47 were related to the differentiation degree, lymph node metastasis and tumor invasion. The survival time of high CRT and CD47 expression group was shorter than that in low expression group(P<0.05). Conclusion CRT and CD47 are potential markers of gastric cancer, which may provide potential targets for the early diagnosis and immunotherapy of gastric cancer.
引文
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[16]Sudo T,Takahashi Y,Sawada G,et al.Significance of CD47expression in gastric cancer[J].Oncol Lett,2017,14(1):801-9.
[17]Yoshida K,Tsujimoto H,Matsumura K,et al.CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer[J].Cancer Med,2015,4(9):1322-33.
[18]邱浩,朱军辉,罗招阳,等.钙网蛋白相关信号通路在肿瘤中的研究进展[J].医学研究杂志,2017,46(5):7-10.[Qiu H,Zhu JH,Luo ZY,et al.Advances in the study of calcium network proteinassociated signaling pathways in tumors[J].Yi Xue Yan Jiu Za Zhi,2017,46(5):7-10.]
[19]Buatois V,Johnson Z,Salgado-Pires S,et al.Preclinical development of a bispecific antibody that safely and effectively targets CD19 and CD47 for the treatment of B cell lymphoma and leukemia[J].Mol Cancer Ther,2018,17(8):1739-51.
[20]Venkateswaran K,Verma A,Bhatt AN,et al.Emerging Roles of Calreticulin in Cancer:Implications for Therapy[J].Curr Protein Pept Sci,2018,19(4):344-57.
[2]Gold LI,Eggleton P,Sweetwyne MT,et al.Calreticulin:nonendoplasmic reticulum functions in physiology and disease[J].FASEB J,2010,24(3):665-83.
[3]Fucikova J,Kasikova L,Truxova I,et al.Relevance of the chaperone-like protein calreticulin for the biological behavior and clinical outcome of cancer[J].Immunol Lett,2018,193:25-34.
[4]Soto-Pantoja DR,Kaur S,Roberts DD,et al.CD47 signaling pathways controlling cellular differentiation and responses to stress[J].Crit Rev Biochem Mol Biol,2015,50(3):212-30.
[5]Zhang X,Chen W,Fan J,et al.Disrupting CD47-SIRPαaxis alone or combined with autophagy depletion for the therapy of glioblastoma[J].Carcinogenesis,2018,39(5):689-99.
[6]Sockolosky JT,Dougan M,Inqram JR,et al.Durable antitumor responses to CD47 blockade req uire ada ptive im m u ne stimulation[J].Proc Natl Acad Sci U S A,2016,113(19):E2646-54.
[7]曲晶磊,徐惠绵,阎影,等.人胃癌组织中分子伴侣蛋白的表达及检测[J].世界华人消化杂志,2005,13(15):1809-13.[Qu JL,Xu HM,Yan Y,et al.Expression of chaperone proteins in human gastric cancer[J].Shi Jie Hua Ren Xiao Hua Za Zhi,2005,13(15):1809-13.]
[8]王妍,周建奖,谢渊,等.钙调蛋白、钙网蛋白及周期蛋白依赖性激酶1基因在胃癌组织中的表达[J].肿瘤防治研究,2013,40(2):151-4.[Wang Y,Zhou JJ,Xie Y,et al.Expression of calmodulin,calcitonin and cyclin-dependent kinase 1 gene in gastric cancer tissue[J].Zhong Liu Fang Zhi Yan Jiu,2013,40(2):151-4.]
[9]Liu SH,Lee WJ,Lai DW,et al.Honokiol confers immunogenicity by dictating calreticulin exposure,activating ER stress and inhibiting epithelial-to-mesenchymal transition[J].Mol Oncol,2015,9(4):834-49.
[10]Sheng W,Chen C,Dong M,et al.Overexpression of calreticulin contributes to the development and progression of pancreatic cancer[J].J Cell Physiol,2014,229(7):887-97.
[11]黄红丽,沈波,杜艳蕾,等.钙网织蛋白在胃癌细胞株中的表达及意义[J].广东医学,2012,33(18):2734-6.[Huang HL,Shen B,Du YL,et al.Expression and significance of calcium mesh protein in gastric cancer cell lines[J].Guangdong Yi Xue,2012,33(18):2734-6.]
[12]黄红丽,聂玉强,李瑜元,等.胃癌组织中钙网蛋白的表达及其与临床病理特征的关系[J].中华生物医学工程杂志,2014,20(3):195-9.[Huang HL,Nie YQ,Li YY,et al.Expression of calreticulin in gastric carcinoma and its correlation with clinicopathology[J].Zhonghua Sheng Wu Yi Xue Gong Cheng Za Zhi,2014,20(3):195-9.]
[13]洪超,高晓明.钙网蛋白的免疫生物学活性研究进展[J].生物物理学报,2012,28(8):621-30.[Hong C,Gao XM.Advances in the study of immunological activity of calcium netting proteins[J].Sheng Wu Wu Li Xue Bao,2012,28(8):621-30.]
[14]Yan JJ,Koo TY,Lee HS,et al.Role of Human CD200Overexpression in Pig-to-Human Xenogeneic Immune Response Compared With Human CD47 Overexpression[J].Transplantation,2018,102(3):406-16.
[15]甘波,杨乐莹,李媛媛,等.CD47和SIRPa1在胃癌组织中的表达和意义[C].首届浙赣两省肿瘤研究交流会论文汇编,杭州:浙江省科学技术协会,2012:361-2.[Gan B,Yang LY,Li YY,et al.Expression and significance of CD47 and SIRPa1in gastric cancer tissues[C].compilation of papers of the first cancer research exchange meeting between zhejiang and jiangxi provinces,Hangzhou:zhejiang provincial association of science and technology,2012:361-2.]
[16]Sudo T,Takahashi Y,Sawada G,et al.Significance of CD47expression in gastric cancer[J].Oncol Lett,2017,14(1):801-9.
[17]Yoshida K,Tsujimoto H,Matsumura K,et al.CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer[J].Cancer Med,2015,4(9):1322-33.
[18]邱浩,朱军辉,罗招阳,等.钙网蛋白相关信号通路在肿瘤中的研究进展[J].医学研究杂志,2017,46(5):7-10.[Qiu H,Zhu JH,Luo ZY,et al.Advances in the study of calcium network proteinassociated signaling pathways in tumors[J].Yi Xue Yan Jiu Za Zhi,2017,46(5):7-10.]
[19]Buatois V,Johnson Z,Salgado-Pires S,et al.Preclinical development of a bispecific antibody that safely and effectively targets CD19 and CD47 for the treatment of B cell lymphoma and leukemia[J].Mol Cancer Ther,2018,17(8):1739-51.
[20]Venkateswaran K,Verma A,Bhatt AN,et al.Emerging Roles of Calreticulin in Cancer:Implications for Therapy[J].Curr Protein Pept Sci,2018,19(4):344-57.