目的: 探讨接头蛋白Crk在胃癌组织中的表达及其与胃癌临床病理因素及预后的关系。方法: 采用免疫组织化学方法检测368例胃癌病人肿瘤组织和配对癌旁组织Crk蛋白表达水平,分析其表达与临床病理因素及预后之间的关系。结果: 与癌旁组织相比,胃癌组织中Crk蛋白表达水平明显升高（P<0.05）。其表达水平与肿瘤大小（P<0.05）、浸润深度（P<0.05）、淋巴结转移（P<0.05）、TNM 分期（P<0.05）密切相关。Crk蛋白表达水平越高,病人预后越差（P<0.05）。多因素分析表明,Crk蛋白是影响胃癌病人预后的独立危险因素。结论: Crk蛋白在胃癌的发生、发展中起重要作用,可作为预测胃癌预后的分子标志物。
冯润华, 毕任达, 陆晟, 袁菲, 许海敏, 刘炳亚, 燕敏, 李琛, 朱正纲
. Crk在胃癌中的表达及其临床意义[J]. 外科理论与实践, 2018
, 23(03)
: 258
-262
.
DOI: 10.16139/j.1007-9610.2018.03.015
Objective: To evaluate the expression of adaptor protein Crk in gastric cancer and the associations with clinicopathological characteristics and prognosis of gastric cancer. Methods: The expression of Crk protein of matched tumor and adjacent tissues in 368 patients with gastric cancer was analyzed by immunohistochemistry. The relation of Crk protein expression with clinicopathological characteristics and clinical outcome was evaluated. Results: Compared with adjacent non-tumor tissues, Crk protein was significantly up-regulated in tumor tissues (P<0.05). An elevated Crk protein expression statistically related with aggressive clinicopathological characteristics significantly including larger tumor size (P<0.05), deeper local invasion (P<0.05), more lymph node metastasis (P<0.05) and advanced TNM stage (P<0.05). Gastric cancer patients with higher expression of Crk protein had poorer prognosis (P<0.05). Multivariate analysis showed that higher level of Crk protein was an independent unfavorable prognostic factor of gastric cancer. Conclusions: Crk protein may be associated with tumor progression in gastric cancer and may predict unfavorable prognosis of gastric cancer as a novel molecular marker.
[1] Ferlay J, Soerjomataram I, Dikshit R, et al.Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015,136(5):E359-E386.
[2] Chen W, Zheng R, Zhang S, et al.Cancer incidence and mortality in China in 2013: an analysis based on urba-nization level[J]. Chin J Cancer Res,2017,29(1):1-10.
[3] Chang SC, Liu KH, Hung CY, et al.Adjuvant chemothe-rapy improves survival in stage Ⅲ gastric cancer after D2 surgery[J]. J Cancer,2018,9(1):81-91.
[4] Kusano T, Shiraishi N, Shiroshita H, et al.Poor prognosis of advanced gastric cancer with metastatic suprapancrea-tic lymph nodes[J]. Ann Surg Oncol,2013,20(7):2290-2295.
[5] Guggenheim DE, Shah MA.Gastric cancer epidemiology and risk factors[J]. J Surg Oncol,2013,107(3):230-236.
[6] Kumar S, Fajardo JE, Birge RB, et al.Crk at the quarter century mark: perspectives in signaling and cancer[J]. J Cell Biochem,2014,115(5):819-825.
[7] Fioretos T, Heisterkamp N, Groffen J, et al.CRK proto-oncogene maps to human chromosome band 17p13[J]. Oncogene,1993,8(10):2853-2855.
[8] Matsuda M, Tanaka S, Nagata S, et al.Two species of human CRK cDNA encode proteins with distinct biological activities[J]. Mol Cell Biol,1992,12(8):3482-3489.
[9] Feller SM.Crk family adaptors-signalling complex formation and biological roles[J]. Oncogene,2001,20(44):6348-6371.
[10] Ren R, Ye ZS, Baltimore D.Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites[J]. Genes Dev,1994,8(7):783-795.
[11] Kar B, Reichman CT, Singh S, et al.Proapoptotic function of the nuclear Crk Ⅱ adaptor protein[J]. Biochemistry,2007,46(38):10828-10840.
[12] Tsuda M, Tanaka S.Roles for crk in cancer metastasis and invasion[J]. Genes Cancer,2012,3(5-6):334-340.
[13] Nishihara H, Tanaka S, Tsuda M, et al.Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers[J]. Cancer Lett,2002,180(1):55-61.
[14] Kumar S, Davra V, E Obr A, et al. Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer[J]. Oncoimmunology,2017,7(1):e1376155.
[15] Matsumoto R, Tsuda M, Wang L, et al.Adaptor protein CRK induces epithelial-mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop[J]. Cancer Sci,2015,106(6):709-717.
[16] Yamada S, Yanamoto S, Kawasaki G, et al.Overexpression of CRKⅡ increases migration and invasive potential in oral squamous cell carcinoma[J]. Cancer Lett,2011,303(2):84-91.
[17] Rodrigues SP, Fathers KE, Chan G, et al.CrkⅠ and CrkⅡ function as key signaling integrators for migration and invasion of cancer cells[J]. Mol Cancer Res,2005,3(4):183-194.
[18] Linghu H, Tsuda M, Makino Y, et al.Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS[J]. Oncogene,2006,25(25):3547-3556.
[19] Dhupkar P, Zhao H, Mujoo K, et al.Crk Ⅱ silencing down-regulates IGF-IR and inhibits migration and invasion of prostate cancer cells[J]. Biochem Biophys Rep,2016,8:382-388.
[20] Elmansuri AZ, Tanino MA, Mahabir R, et al.Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer[J]. Oncotarget,2016,7(19):27094-27107.
[21] Suzuki M, Mimuro H, Suzuki T, et al.Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion[J]. J Exp Med,2005,202(9):1235-1247.
[22] Feng R, Chen X, Yu Y, et al.miR-126 functions as a tumour suppressor in human gastric cancer[J]. Cancer Lett,2010,298(1):50-63.
