Clinical significance of h-TERT and c-Met expression in the peripheral blood circulation of pancreatic cancer patients
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摘要:
目的 探讨胰腺癌患者外周血循环肝细胞生长因子受体c-Met和端粒酶亚催化单位(human telomerase reverse transcriptase, h-TERT)表达的临床意义。 方法 联合应用纳米免疫磁珠及巢式PCR方法检测胰腺癌患者外周血循环中c-Met和h-TERT的表达以确定微转移是否存在, 并探讨其临床意义。 结果 胰腺癌患者外周血循环c-Met与h-TERT的表达与性别、年龄、肿瘤大小、血清CA-199及CEA无统计学相关(P > 0.05)。不同肿瘤分期间c-Met和h-TERT阳性表达率有显著性差异(P < 0.05), 外周血c-Met与h-TERT表达阳性患者有肿瘤复发风险, h-TERT阳性患者较c-Met阳性患者肿瘤复发率高(P < 0.05)。c-Met表达阳性的患者无瘤生存中位时间为12个月, 阴性患者为20个月(P=0.044);h-TERT表达阳性患者无瘤生存中位时间为9个月, 阴性患者为15个月(P < 0.001)。 结论 外周血存在微转移的胰腺癌患者肿瘤复发率高, 外周血h-TERT较c-Met表达阳性患者肿瘤复发率高, 预后更差。 Abstract:Objective This study aimed to investigate the clinical significance of the human telomerase reverse transcriptase(h-TERT) and c-Met gene expressions in the peripheral blood of pancreatic cancer patients. Methods Magnetic cell sorting and reverse transcription-nest-polymerase chain reaction were performed to detect h-TERT and c-Met expressions in the peripheral blood of pancreatic cancer and determine whether or not micrometastasis was present. The clinical significance of micrometastasis was analyzed. Results The positive rates of c-Met and h-TERT did not significantly correlate with gender, age, cancer size, cancer antigen 19-9, and carcinoembryonic antigen in the serum(P > 0.05). The positive rates of c-Met and h-TERT genes in the peripheral blood of pancreatic cancer patients significantly correlated with TNM staging(P < 0.05). The recurrence rate was higher in pancreatic cancer patients with positive h-TERT compared with that in patients with positive c-Met. The median disease-free survival time for patients with positive h-TERT and c-Met was 12 and 9 months, respectively. The median disease-free survival time was 20 months(P=0.044) for patients with negative h-TERT. For pancreatic cancer patients with negative c-Met, the median disease-free survival time was 15 months(P < 0.001). Conclusion The prognosis is poorer in h-TERT-positive patients than in c-Met-positive patients. The relapse rate was higher in h-TERT-positive patients who have poor prognosis. -
Key words:
- pancreatic cancer /
- micrometastasis /
- c-Met /
- h-TERT
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图 1 h-TERT在外周血循环中的表达
Figure 1. Positive rates of h-TERT in the peripheral blood circulation
1: Negative; 2 to 5: Positive
图 2 c-Met在外周血循环中的表达
Figure 2. Positive rates of c-Met in the peripheral blood circulation
1: Negative; 2 to 3: Positive; 4: Negative; 5: Positive
图 3 c-Met表达阳性患者的术后生存率
Figure 3. Postoperative survival rates of c-Met-positive patients
图 4 h-TERT表达阳性患者的术后生存率
Figure 4. Postoperative survival rates of h-TERT-positive patients
表 1 引物序列及产物扩增长度
Table 1. Primer sequences and amplification primer length
表 2 胰腺癌患者外周血循环c-Met和h-TERT基因的表达与临床参数的关系
Table 2. Relationship of the expression of h-TERT and c-Met genes in the peripheral blood circulation with the clinical parameters
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[1] Yekebas EF, Bogoevski D, Bubenheim M, et al. Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy[J]. World J Gastroenterol, 2006, 12(40): 6515-6521. doi: 10.3748/wjg.v12.i40.6515 [2] Zhao L, Mou DC, Peng JR, et al. Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients[J]. World J Gastroenterol, 2010, 16(32): 4072-4078. doi: 10.3748/wjg.v16.i32.4072 [3] Muto Y, Matubara H, Tanizawa T, et al. Rapid diagnosis of micrometastasis of gastric cancer using reverse transcription loop-mediated isothermal amplification[J]. Oncol Rep, 2011, 26(4): 789-794. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM21769432 [4] Paterlini-Brechot P, Benali NL. Circulating tumour cells (CTC) detection: clinical impact and future directions[J]. Cancer Lett, 2007, 253(2): 180-204. doi: 10.1016/j.canlet.2006.12.014 [5] Kumari A, Srinivasan R, Vasishta RK, et al. Positive regulation of human telomerase reverse transcriptase gene expression and telomerase activity by DNA methylation in pancreatic cancer[J]. Ann Surg Oncol, 2009, 16(4): 1051-1059. doi: 10.1245/s10434-009-0333-8 [6] 胡亮, 周家华, 余泽前, 等. 纳米免疫磁珠联合RT-nest-PCR法检测胰腺癌外周血微转移的敏感度及特异性[J]. 东南大学学报(医学版), 2009, 28(4): 287-290. doi: 10.3969/j.issn.1671-6264.2009.04.012 [7] Zhou J, Hu L, Yu Z, et al. Marker expression in circulating cancer cells of pancreatic cancer patients. [J]. J Surg Res, 2011, 171(2): 631-636. doi: 10.1016/j.jss.2010.05.007 [8] Antoniou KM, Margaritopoulos GA, Proklou A, et al. Investigation of telomerase/telomeres system in bone marrow mesenchymal stem cells derived from IPF and RA-UIP[J]. J Inflamm (Lond), 2012, 9(1): 27. doi: 10.1186/1476-9255-9-27 [9] Grochola LF, Greither T, Taubert HW, et al. Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the pancreas[J]. Neoplasia, 2008, 10(9): 973-976. doi: 10.1593/neo.08578 [10] Lee JH, Khadka P, Baek SH, et al. CHIP promotes human telomerase reverse transcriptase degradation and negatively regulates telomerase activity[J]. J Biol Chem, 2010, 285(53): 42033-42045. doi: 10.1074/jbc.M110.149831 [11] Chrysovergis A, Gorgoulis VG, Giotakis I, et al. Simultaneous over activation of EGFR, telomerase (h-TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis[J]. Med Oncol, 2011, 28(3): 871-877. doi: 10.1007/s12032-010-9522-3 [12] Miyamoto M, Ojima H, Iwasaki M, et al. Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma[J]. Br J Cancer, 2011, 105(1): 131-138. doi: 10.1038/bjc.2011.199 [13] Oh YM, Song YJ, Lee SB, et al. A new anti-c-met antibody selected by a mechanism-based dual-screening method: therapeutic potential in cancer[J]. Mol Cells, 2012, 34(6): 523-529. doi: 10.1007/s10059-012-0194-z [14] Herreros-Villanueva M, Zubia-Olascoaga A, Bujanda L. c-Met in pancreatic cancer stem cells: therapeutic implications[J]. World J Gastroenterol, 2012, 18(38): 5321-5323. doi: 10.3748/wjg.v18.i38.5321 [15] Gardian K, Janczewska S, Olszewski WL, et al. Analysis of pancreatic cancer microenvironment: role of macrophage infiltrates and growth factors expression[J]. J Cancer, 2012, 3: 285-291. doi: 10.7150/jca.4537 -
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