自噬相关蛋白 Beclin-1 和 LC3 预测西妥昔单抗在晚期结直肠癌中的疗效。
Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer.
机构信息
State Key Laboratory of Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China.
出版信息
World J Gastroenterol. 2011 Nov 21;17(43):4779-86. doi: 10.3748/wjg.v17.i43.4779.
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.
目的
探讨自噬相关蛋白 Beclin-1 和 LC3 在预测晚期结直肠癌（ACRC）患者接受西妥昔单抗疗效中的作用。
方法
本研究纳入了中山大学肿瘤防治中心 2005 年 3 月 1 日至 2008 年 12 月 31 日收治的 85 例 ACRC 患者的数据，包括 45 例接受西妥昔单抗联合化疗和 40 例接受非西妥昔单抗联合化疗的患者。采用免疫组化法检测 Beclin-1 和 LC3 的表达，聚合酶链反应法检测 KRAS 状态。
结果
ACRC 中 Beclin-1 和 LC3 的表达呈显著正相关（r = 0.44，P < 0.01）；然而，LC3 在癌组织中的表达高于正常组织（Z = -2.63，P < 0.01）。在接受西妥昔单抗联合化疗的患者中，LC3 低表达患者的客观缓解率（ORR）高于 LC3 高表达患者（52.9%比 17.9%，P = 0.01），Beclin-1 低表达患者的中位无进展生存期（PFS）长于 Beclin-1 高表达患者（9.0 个月比 3.0 个月，P = 0.01）。然而，在接受非西妥昔单抗联合化疗的患者中，这些预测关系均未检测到。在接受西妥昔单抗联合化疗的患者中，KRAS 野生型患者的 ORR（42.3%比 9.1%，P = 0.049）和疾病控制率（DCR）（73.1%比 36.4%，P = 0.035）更高，中位 PFS 更长（5.5 个月比 2.5 个月，P = 0.02），而 KRAS 突变型患者的 ORR 和 DCR 均较低（P = 0.52），中位 PFS 也较短（P = 0.32）。Beclin-1（P = 0.52）和 LC3（P = 0.32）的表达与 KRAS 状态均无显著相关性。
结论
在接受西妥昔单抗联合化疗的 ACRC 患者中，Beclin-1 低表达患者的 PFS 长于 Beclin-1 高表达患者，LC3 低表达患者的 ORR 更高。
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