Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.
Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.
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DOI：
10.1002/ijc.29496
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发表时间：
2015-09-15
影响因子：
6.4
通讯作者：
Sinicrope, Frank A.
中科院分区：
文献类型：
--
作者：
Zaanan, Aziz;Park, Jae Myung;Tougeron, David;Huang, Shengbing;Wu, Tsung-Teh;Foster, Nathan R.;Sinicrope, Frank A.
Beclin 1是细胞应激诱导的自噬的重要调节因子，在已建立的肿瘤中用于维持细胞存活。我们最近证实Beclin-1抑制可以使结直肠癌细胞对辐射诱导的DNA损伤和凋亡敏感。因此，我们推测Beclin 1的表达水平可能与体内的辐射敏感性有关。我们在手术切除标本中确定了治疗前直肠癌组织中Beclin 1的表达与新辅助化疗的反应之间的关系。连续的II期和III期直肠腺癌患者(n=96)接受新辅助化疗和外科手术治疗。免疫组织化学方法检测BECLIN-1的表达，并将其表达水平分为低、高两组。我们分别确定了56例(58.3%)和40例(41.7%)患者Beclin-1的高表达和低表达。Beclin 1高表达患者与低Beclin 1表达患者在放化疗后降期的可能性显著降低[45%(25/55)比58%(22/38)；p=0.02]。在调整了年龄、性别、组织学分级和基线TNM分期的多变量分析中，Beclin 1的表达对肿瘤降期的影响仍然具有统计学意义(p=0.03)。Beclin 1的表达水平与放化疗后肿瘤降期率的关系与体外实验数据一致，提示Beclin 1可能是预测直肠癌放化疗疗效的生物标志物。
Beclin 1 is an essential regulator of autophagy that is induced in response to cellular stress and serves to maintain cell survival in established tumors. We recently demonstrated that Beclin 1 suppression can sensitize colorectal cancer cells to radiation-induced DNA damage and apoptosis. Therefore, we hypothesized that the level of Beclin 1 expression may be associated with radiation sensitivity in vivo. We determined the association of Beclin 1 expression in pre-treatment rectal cancer tissues with response to neoadjuvant chemoradiation in surgical resection specimens. Consecutive stage II and III (n=96) rectal adenocarcinoma patients were treated with neoadjuvant chemoradiation followed by surgical resection with curative intent. Beclin 1 was analyzed by immunohistochemistry and the expression level was dichotomized at the median value with categorization into low and high groups. We identified 56 (58.3%) and 40 (41.7%) patients with high vs low level Beclin 1 expression, respectively. Patients with high vs low Beclin 1 expression were significantly less likely to be downstaged after chemoradiation treatment [45% (25/55) vs 58% (22/38); p=0.02]. In a multivariable analysis adjusted for age, sex, histological grade and baseline TNM stage, the impact of Beclin 1 expression on tumor downstaging remained statistically significant (p=0.03). The association of the level of Beclin 1 expression with the rate of tumor downstaging after chemoradiation is consistent with in vitro data, and suggests that Beclin 1 may be a predictive biomarker for the efficacy of chemoradiation in rectal cancer patients.
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影响因子：
168.9
作者：
Sebag-Montefiore, David;Stephens, Richard J.;Steele, Robert;Monson, John;Grieve, Robert;Khanna, Subhash;Quirke, Phil;Couture, Jean;de Metz, Catherine;Myint, Arthur Sun;Bessell, Eric;Griffiths, Gareth;Thompson, Lindsay C.;Parmar, Mahesh
通讯作者：
Parmar, Mahesh
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影响因子：
4.6
作者：
Sui X;Kong N;Wang X;Fang Y;Hu X;Xu Y;Chen W;Wang K;Li D;Jin W;Lou F;Zheng Y;Hu H;Gong L;Zhou X;Pan H;Han W
通讯作者：
Han W
影响因子：
8.4
作者：
Li, Jie;Hou, Ni;Kuwano, Hiroyuki
通讯作者：
Kuwano, Hiroyuki
影响因子：
158.5
作者：
Sauer, R;Becker, H;Raab, R
通讯作者：
Raab, R
DOI：
10.1097/00000421-200104000-00001
发表时间：
2001-04-01
影响因子：
2.6
作者：
Janjan, NA;Crane, C;Skibber, J
通讯作者：
Skibber, J