Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer

Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer
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自噬相关蛋白 Beclin-1 和 LC3 预测西妥昔单抗对晚期结直肠癌的疗效

DOI:
10.3748/wjg.v17.i43.4779
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发表时间:
2011-11-21
影响因子:
4.3
通讯作者:
Xia, Liang-Ping
Xia, Liang-Ping
中科院分区:
医学2区
文献类型:
--
作者:
Guo, Gui-Fang;Jiang, Wen-Qi;Xia, Liang-Ping

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目的:探讨自噬相关蛋白Beclin-1和LC3在预测西妥昔单抗治疗晚期结直肠癌(ACRC)疗效中的作用。方法:对2005年3月1日至2008年12月31日在中山大学肿瘤研究中心收治的85例ACRC患者的临床资料进行分析,其中含西妥昔单抗化疗45例,非西妥昔单抗化疗40例。结果:Beclin-1和Lc3在癌组织中的表达显著相关(r=0.44,P<0.01),而Lc3在癌组织中的表达明显高于正常组织(Z=-2.63,P<0.01)。西妥昔单抗低表达患者客观有效率(ORRs)高于高表达患者(52.9%比17.9%,P=0.01),Beclin-1低表达患者中位无进展生存期(PFS)长于Beclin-1高表达患者(9.0mo比3.0mo,P=0.01)。然而,在接受非西妥昔单抗化疗的患者中,没有检测到这两种预测关系。在含西妥昔单抗的化疗组中,野生型KRAS患者的ORR(42.3%比9.1%,P=0.049)和疾病控制率(73.1%VS 36.4%,P=0.035)和中位PFS(5.5mo比2.5mo,P=0.035)均高于突变KRAS患者。Beclin-1(P=0.52)和LC3(P=0.32)的表达与KRAS状态无关。结论:在接受西妥昔单抗化疗的ACRC患者中,Beclin-1低表达患者的PFS长于Beclin-1高表达患者,而LC3低表达患者的ORR更高。(C)2011年白石登。版权所有。
AIM: To investigate the utility of Beclin-1 and LC3, two autophagy-related proteins, in predicting the cetuximab efficacy in advanced colorectal cancer (ACRC).METHODS: The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1, 2005 to December 31, 2008 were studied, including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression was evaluated by immunohistochemistry, and KRAS status was evaluated by polymerase chain reaction.RESULTS: Beclin-1 and LC3 expression in ACRC was significantly correlated (r = 0.44, P < 0.01); however, LC3 was more highly expressed in cancerous tissues than in normal tissues (Z = -2.63, P < 0.01). In the cetuximab-containing chemotherapy group, patients with low LC3 expression had higher objective response rates (ORRs) than those with high LC3 expression (52.9% vs 17.9%, P = 0.01), and patients with low Beclin-1 expression had a longer median progression-free survival (PFS) than their counterparts with higher Beclin-1 expression (9.0 mo vs 3.0 mo, P = 0.01). However, neither of these predictive relationships was detected in the group treated with non-cetuximab-containing chemotherapy. Patients with wild-type KRAS had higher ORRs (42.3% vs 9.1%, P = 0.049) and disease control rates (DCRs) (73.1% vs 36.4%, P = 0.035), and longer median PFS (5.5 mo vs 2.5 mo, P = 0.02) than those with mutant KRAS in the cetuximab-containing chemotherapy group. Neither Beclin-1 (P = 0.52) nor LC3 (P = 0.32) expression was significantly correlated with KRAS status.CONCLUSION: Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression, and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy. (C) 2011 Baishideng. All rights reserved.