CLIC4, ERp29, and Smac/DIABLO Derived from Metastatic Cancer Stem-like Cells Stratify Prognostic Risks of Colorectal Cancer
CLIC4, ERp29, and Smac/DIABLO Derived from Metastatic Cancer Stem-like Cells Stratify Prognostic Risks of Colorectal Cancer
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源自转移性癌症干细胞的 CLIC4、ERp29 和 Smac/DIABLO 对结直肠癌的预后风险进行分层
DOI：
10.1158/1078-0432.ccr-13-1887
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发表时间：
2014-07-15
影响因子：
11.5
通讯作者：
Ding, Yan-Qing
中科院分区：
文献类型：
--
作者：
Deng, Yong-Jian;Tang, Na;Ding, Yan-Qing
目的：肿瘤干细胞样细胞与肿瘤的复发和转移密切相关，但与肿瘤干细胞样细胞和肿瘤转移相关的生物标志物对结直肠癌预后的影响尚不清楚。实验设计：我们从结直肠癌转移性肿瘤干细胞样细胞中鉴定了CLIC 4、ERp29和Smac/DIABLO三种蛋白，并验证了这些蛋白在肿瘤转移行为中的作用。通过IHC检测训练队列中接受根治性手术的结直肠癌患者的结直肠癌肿瘤和匹配的结肠粘膜中的蛋白质。评估蛋白质表达水平与五年疾病特异性生存期（DSS）之间的关联，以预测421例训练队列和228例验证队列的生存概率。一个包括CLIC 4、ERp29和Smac/DIABLO的三蛋白组，其通过从训练队列中排除临床病理学特征而从多变量分析中产生，将结直肠癌患者分为极低、低、中、高风险组，5年DSS概率差异有统计学意义（88.6%、63.3%、30.4%、11.4%; P <0.001）。该小组独立于肿瘤淋巴结转移分期系统和组织学分级来预测预后，并且还能够将验证队列分为四个风险分层（5年DSS概率分别为98.2%、80.2%、25.6%和2.7%; P <0.001）。CLIC 4、ERp29和Smac/DIABLO整合到一个基于与转移相关的癌症干细胞样细胞的新面板中，对结直肠癌的预后风险进行分层。分子标记物预测结直肠癌术后的危险性，有助于临床医生对结直肠癌术后患者进行个体化管理。(C)2014年AACR。
Purpose: Cancer stem-like cells have been well accepted to be involved in recurrence and metastasis of cancers, but the prognostic potential of biomarkers integrating with metastasis and cancer stem-like cells for colorectal cancer is unclear.Experimental Design: We identified three proteins, CLIC4, ERp29, and Smac/DIABLO, from metastatic cancer stem-like cells of colorectal cancer and verified the proteins' role in metastatic behaviors. The proteins were detected by IHC in colorectal cancer tumors and matched colonic mucosa from patients with colorectal cancer who underwent radical surgery in the training cohort. The associations between proteins expression levels and five-year disease-specific survival (DSS) were evaluated to predict the survival probability in the training cohort of 421 cases and the validation cohort of 228 cases.Results: A three-protein panel including CLIC4, ERp29, and Smac/DIABLO, which was generated from multivariate analysis by excluding clinicopathologic characteristics from the training cohort, distinguished patients with colorectal cancer into very low-, low-, middle-, and high-risk groups with significant differences in five-year DSS probability (88.6%, 63.3%, 30.4%, 11.4%; P < 0.001). The panel is independent from tumor-node-metastasis staging system and histologic grading to predict prognosis, and also enables classification of validation cohort into four risk stratifications (five-year DSS probability is 98.2%, 80.2%, 25.6%, and 2.7%; P < 0.001).Conclusions: CLIC4, ERp29, and Smac/DIABLO integrated into a novel panel based on cancer stem-like cells in association with metastasis stratify the prognostic risks of colorectal cancer. Prediction of risks with molecular markers will benefit clinicians to make decisions of individual management with postoperative colorectal cancer patients. (C) 2014 AACR.