GDF15和MMP7的表达与胃癌临床病理特征及其预后的相关性
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摘要
目的探讨GDF15和MMP7的表达与胃癌及其预后的相关性。方法研究所需样本组织收集自重庆市黔江中心医院2014年6月至2016年3月胃癌术后标本作为研究材料。采用实时荧光定量聚合酶链反应(qRT-PCR)、免疫印迹(Western blot)和免疫组织化学法(immunohistochemistry)检测胃癌组织及对应癌旁组织中GDF15和MMP7的表达。结果与正常癌旁组织相比,胃癌组织中GDF15和MMP7 mRNA和蛋白表达水平均升高。GDF15在胃癌中阳性表达率为73. 58%,高于癌旁组织中的阳性表达率26. 32%(P <0. 01); MMP7在胃癌中阳性表达率为78. 30%,高于癌旁组织的阳性表达率46. 32%(P <0. 01)。GDF15表达与肿瘤直径有关(P <0. 05),MMP7表达均与胃癌有无淋巴结转移和TNM分期相关(P <0. 01)。单因素生存分析显示,GDF15和MMP7阳性表达均与胃癌患者生存时间呈负相关(P <0. 05)。结论 GDF15和MMP7是有效的胃癌预后标志物。
Objective To investigate the expression of GDF15 and MMP7 in gastric carcinoma and its relationship with clinicopathological characteristics and prognosis. Methods The samples of gastric carcinoma were collected from Qianjiang Central Hospital of Chongqing from June 2014 to March 2016. The expression levels of GDF15 and MMP7 in gastric cancer and its adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction( qRT-PCR),Western blot and immunohistochemistry. Results Compared with normal adjacent tissues,the mRNA and protein expression levels of GDF15 and MMP7 in gastric cancer tissues were increased. The positive expression rate of GDF15 was higher in gastric cancer than in adjacent tissues( 73. 58% vs 26. 32%,P <0. 01). The positive expression rate of MMP7 was higher in gastric cancer than in adjacent tissues( 78. 30% vs 46. 32%,P < 0. 01).The expression of GDF15 was related to the diameter of tumors( P < 0. 05). The expression of MMP7 was correlated with lymph node metastasis and TNM stage in gastric cancer( P < 0. 01). Univariate survival analysis showed that the positive expression of GDF15 and MMP7 was negatively correlated with the survival time of gastric cancer patients( P < 0. 05). Conclusion GDF15 and MMP7 may be effective prognostic markers for gastric carcinoma.
Objective To investigate the expression of GDF15 and MMP7 in gastric carcinoma and its relationship with clinicopathological characteristics and prognosis. Methods The samples of gastric carcinoma were collected from Qianjiang Central Hospital of Chongqing from June 2014 to March 2016. The expression levels of GDF15 and MMP7 in gastric cancer and its adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction( qRT-PCR),Western blot and immunohistochemistry. Results Compared with normal adjacent tissues,the mRNA and protein expression levels of GDF15 and MMP7 in gastric cancer tissues were increased. The positive expression rate of GDF15 was higher in gastric cancer than in adjacent tissues( 73. 58% vs 26. 32%,P <0. 01). The positive expression rate of MMP7 was higher in gastric cancer than in adjacent tissues( 78. 30% vs 46. 32%,P < 0. 01).The expression of GDF15 was related to the diameter of tumors( P < 0. 05). The expression of MMP7 was correlated with lymph node metastasis and TNM stage in gastric cancer( P < 0. 01). Univariate survival analysis showed that the positive expression of GDF15 and MMP7 was negatively correlated with the survival time of gastric cancer patients( P < 0. 05). Conclusion GDF15 and MMP7 may be effective prognostic markers for gastric carcinoma.
引文
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[13] Ishige T,Nishimura M,Satoh M,et al. Combined secretomicsand transcriptomics revealed cancer-derived GDF15 is involved indiffuse-type gastric cancer progression and fibroblast activation[J]. Sci Rep,2016,6(2):21681.
[14] Mao D,Zhang Y,Lu H,et al. Molecular basis underlying inhi-bition of metastasis of gastric cancer by anti-VEGFa treatment[J]. Tumour Biol,2014,35(8):8217-8223.
[15] Wu Q,Li X,Yang H,et al. Extracellular matrix protein 1 iscorrelated to carcinogenesis and lymphatic metastasis of humangastric cancer[J]. World J Surg Oncol,2014,12(8):132.
[16] Koskensalo S,Mrena J,Wiksten JP,et al. MMP-7 overexpres-sion is an independent prognostic marker in gastric cancer[J].Tumour Biol,2010,31(3):149-155.
[17] Sentani K,Matsuda M,Oue N,et al. Clinicopathological signifi-cance of MMP-7,lamininγ2 and EGFR expression at the inva-sive front of gastric carcinoma[J]. Gastric Cancer,2014,17(3):412-422.
[18] Wu D. Isocitrate dehydrogenase 2 inhibits gastric cancer cell in-vasion via matrix metalloproteinase 7[J]. Tumor Biol,2015,37(4):5225-5230.
[19] Ye Y,Zhou X,Li X,et al. Inhibition of epidermal growth factorreceptor signaling prohibits metastasis of gastric cancer via down-regulation of MMP7 and MMP13[J]. Tumour Biol,2014,35(11):10891-10896.
[20] Suarez MI,Uribe D,Jaramillo CM,et al. Wnt/beta-catenin sig-naling pathway in hepatocellular carcinomas cases from Colombia[J]. Ann Hepatol,2015,14(1):64-74.
[2] Chen Z,Lin L,Cheng X,et al. Treatment of gastric cancer cellswith nonthermal atmospheric plasma generated in water[J].Biointerphases,2016,11(3):031010.
[3] Hsu TI,Lin SC,Lu PS,et al. MMP7-mediated cleavage of nu-cleolin at Asp255 induces MMP9 expression to promote tumormalignancy[J]. Oncogene,2015,34(7):826-837.
[4] Grindel BJ,Martinez JR,Pennington CL,et al. Matrilysin/ma-trix metalloproteinase-7(MMP7)cleavage of perlecan/HSPG2creates a molecular switch to alter prostate cancer cell behavior[J]. Matrix Biol,2014,36(6):64-76.
[5] Liu G,Jiang C,Li D,et al. MiRNA-34a inhibits EGFR-signa-ling-dependent MMP7 activation in gastric cancer[J]. TumourBiol,2014,35(10):9801-9806.
[6] Urakawa N,Utsunomiya S,Nishio M,et al. GDF15 derivedfrom both tumor-associated macrophages and esophageal squa-mous cell carcinomas contributes to tumor progression via Akt andErk pathways[J]. Lab Invest,2015,95(5):491-503.
[7] Blancocalvo M,Tarrío N,Reboredo M,et al. Circulating levelsof GDF15,MMP7 and miR-200c as a poor prognostic signature ingastric cancer[J]. Future Oncol,2016,10(7):1187-1202.
[8] Cavatorta O,Scida S,Miraglia C,et al. Epidemiology of gastriccancer and risk factors[J]. Acta Biomed,2018,89(8-S):82-87.
[9] Lee J,Fricke F,Warnken U,et al. Reconstitution of TGFBR2-mediated signaling causes upregulation of GDF-15 in HCT116Colorectal Cancer Cells[J]. PLo S One 2015, 26(6):e0131506.
[10] Guo H,Dai Y,Wang A,et al. Association between expressionof MMP-7 and MMP-9 and pelvic lymph node and para-aorticlymph node metastasis in early cervical cancer[J]. J ObstetGynaecol Res,2018,44(7):1274-1283.
[11] Skipworth RJ,Deans DA,Tan BH,et al. Plasma MIC-1 corre-lates with systemic inflammation but is not an independent deter-minant of nutritional status or survival in oesophago[J]. Br JCancer,2010,102(4):665-672.
[12] Baek KE,Yoon SR,Kim JT,et al. Upregulation and secretionof macrophage inhibitory cytokine-1(MIC-1)in gastric cancers[J]. Clin Chim Acta,2009,401(1-2):128-133.
[13] Ishige T,Nishimura M,Satoh M,et al. Combined secretomicsand transcriptomics revealed cancer-derived GDF15 is involved indiffuse-type gastric cancer progression and fibroblast activation[J]. Sci Rep,2016,6(2):21681.
[14] Mao D,Zhang Y,Lu H,et al. Molecular basis underlying inhi-bition of metastasis of gastric cancer by anti-VEGFa treatment[J]. Tumour Biol,2014,35(8):8217-8223.
[15] Wu Q,Li X,Yang H,et al. Extracellular matrix protein 1 iscorrelated to carcinogenesis and lymphatic metastasis of humangastric cancer[J]. World J Surg Oncol,2014,12(8):132.
[16] Koskensalo S,Mrena J,Wiksten JP,et al. MMP-7 overexpres-sion is an independent prognostic marker in gastric cancer[J].Tumour Biol,2010,31(3):149-155.
[17] Sentani K,Matsuda M,Oue N,et al. Clinicopathological signifi-cance of MMP-7,lamininγ2 and EGFR expression at the inva-sive front of gastric carcinoma[J]. Gastric Cancer,2014,17(3):412-422.
[18] Wu D. Isocitrate dehydrogenase 2 inhibits gastric cancer cell in-vasion via matrix metalloproteinase 7[J]. Tumor Biol,2015,37(4):5225-5230.
[19] Ye Y,Zhou X,Li X,et al. Inhibition of epidermal growth factorreceptor signaling prohibits metastasis of gastric cancer via down-regulation of MMP7 and MMP13[J]. Tumour Biol,2014,35(11):10891-10896.
[20] Suarez MI,Uribe D,Jaramillo CM,et al. Wnt/beta-catenin sig-naling pathway in hepatocellular carcinomas cases from Colombia[J]. Ann Hepatol,2015,14(1):64-74.