Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer
Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer
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DOI：
10.1016/j.yexmp.2015.03.029
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Li, Chien-Feng
中科院分区：
文献类型：
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作者：
He, Hong-Lin;Lee, Ying-En;Li, Chien-Feng
已经发现与蛋白质折叠相关的基因在癌症的子集中具有一定的预后意义。本研究的目的是评估手术后接受新辅助同步放化疗（CCRT）的直肠癌患者中DNAJC 12表达的临床影响。通过对直肠癌公共转录组数据集的数据挖掘，我们发现，HSP 40/DNAJ家族成员DNAJC 12是与CCRT反应相关的最重要的基因。我们进一步用免疫组化法检测了172例直肠癌患者治疗前肿瘤标本中DNAJC 12的表达。从这个集合中，我们统计分析了DNAJC 12表达与各种临床病理因素、肿瘤消退分级、总生存期（OS）、无病生存期（DFS）和局部无复发生存期（LRFS）的相关性。DNAJC 12的高表达与治疗前和治疗后的晚期肿瘤状态（P < 0.001）、治疗前和治疗后的晚期淋巴结状态（P <0.001）、血管浸润增加（P = 0.015）、神经周围浸润增加（P = 0.023）和较低的肿瘤消退等级（P = 0.009）显著相关。更重要的是，发现DNAJC 12高表达与OS（P = 0.0012）、DFS（P < 0.0001）和LRFS（P = 0.0001）的不良预后相关。多因素分析显示，DNAJC 12过表达仍是缩短OS（P = 0.040）、DFS（P < 0.001）和LRFS（P = 0.016）的独立危险因素。数据表明，DNAJC 12过表达作为新辅助CCRT反应的阴性预测因子，与接受新辅助CCRT后手术的直肠癌患者的生存期缩短显著相关。(C)2015 Elsevier Inc. All rights reserved.
Genes associated with protein folding have been found to have certain prognostic significance in a subset of cancers. The aim of this study is to evaluate the clinical impact of DNAJC12 expression in patients with rectal cancers receiving neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. Through data mining from a public transcriptomic dataset of rectal cancer focusing on genes associated with protein folding, we found that DNAJC12, a member of the HSP40/DNAJ family, was the most significant such gene correlated with the CCRT response. We further evaluated the expression of DNAJC12 by immunohistochemistly in the pre-treatment tumor specimens from 172 patients with rectal cancers. From this set, we statistically analyzed the association of DNAJC12 expression with various clinicopathological factors, tumor regression grade, overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS). High expression of DNAJC12 was significantly associated with advanced pre- and post-treatment tumor status (P < 0.001), advanced pre- and post-treatment nodal status (P < 0.001), increased vascular invasion (P = 0.015), increased perineural invasion (P = 0.023) and lower tumor regression grade (P = 0.009). More importantly, high expression of DNAJC12 was found to be correlated with poor prognosis for OS (P = 0.0012), DFS (P < 0.0001) and LRFS (P = 0.0001). In multivariate analysis, DNAJC12 overexpression still emerged as an independent prognosticator for shorter OS (P = 0.040), DFS (P < 0.001) and LRFS (P = 0.016). The data indicate that DNAJC12 overexpression acts as a negative predictive factor for the response to neoadjuvant CCRT and was significantly associated with shorter survival in patients with rectal cancers receiving neoadjuvant CCRT followed by surgery. (C) 2015 Elsevier Inc. All rights reserved.