KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer
KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer
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DOI：
10.1158/1078-0432.ccr-07-0393
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发表时间：
2007-06-01
影响因子：
11.5
通讯作者：
Gallie, Brenda L.
中科院分区：
文献类型：
--
作者：
Corson, Timothy W.;Zhu, Chang Qi;Gallie, Brenda L.
目的：有丝分裂驱动蛋白 KIF14 在包括肺癌在内的多种癌症中过度表达。因此，我们研究了 KIF14 表达与临床变量的关系以及 KIF14 对非小细胞肺癌体外集落形成的影响。实验设计：从 129 个未经治疗的切除肿瘤中提取 RNA，并通过实时逆转录 PCR 定量 KIF14 表达。通过标准统计方法确定与临床变量的关联。 H1299 和 HeLa 细胞中 KIF14 的表达被小干扰 RNA 敲低；结果：鳞状细胞癌中KIF14水平最高，其次是大细胞未分化癌，最后是腺癌（P=0.002）。 KIF14水平随着分化而降低（P = 0.01），但与病理分期、Tor N分期或性别无关。当对中位数进行二分时，KIF14 过度表达显着降低了无病生存率（Kaplan-Meier log-rank，P = 0.01），并且有降低总生存率的趋势（P = 0.08）。在单变量 Cox 比例风险回归中，增加 KIF14 表达会降低无病生存率 [P = 0.01；风险比，1.44（95%置信区间，1.09-1.91）]。在多变量 Cox 回归中，包括分期、分化、组织学和肿瘤纯度作为协变量，KIF14 过表达仍然是无病生存的独立预后因素 [P = 0.01；风险比，1.45（95% 置信区间，1.09-1.94）]。在非小细胞肺癌和宫颈癌细胞系中敲低 KIF14 会减少软琼脂中的增殖和集落形成。结论：KIF14 表达是肺癌无病生存的独立预后因素，敲低会降低体外致瘤性，表明它是一种临床相关的癌基因，也是一个值得进一步研究的令人兴奋的治疗靶点。
Purpose: The mitotic kinesin KIF14 is overexpressed in multiple cancers including lung cancer. Therefore, we investigated KIF14 expression in association with clinical variables and the effect of KIF14 on in vitro colony formation in non - small-cell lung carcinoma.Experimental Design: RNA was extracted from 129 untreated, resected tumors and KIF14 expression was quantified by real-time reverse transcription-PCR. Associations with clinical variables were determined by standard statistical methods. KIF14 expression was knocked down by small interfering RNA in H1299 and HeLa cells; proliferation and growth in soft agar were assayed.Results: Squamous cell carcinoma had the highest KIF14 level, followed by large-cell undifferentiated carcinoma, then adenocarcinoma (P = 0.002). KIF14 level decreased with differentiation (P = 0.01) but was not associated with pathologic stage,Tor N stage, or sex. When dichotomized about the median, KIF14 overexpression significantly decreased disease-free survival (Kaplan-Meier log-rank, P = 0.01) and trended toward decreasing overall survival (P = 0.08). In a univariate Cox proportional hazard regression, increasing KIF14 expression decreased disease-free survival [P = 0.01; hazard ratio, 1.44 (95% confidence interval, 1.09-1.91)]. In a multivariate Cox regression, including stage, differentiation, histology, and tumor purity as covariates, KIF14 overexpression remained an independent prognostic factor for disease-free survival [P = 0.01; hazard ratio, 1.45 (95% confidence interval, 1.09-1.94)]. Knockdown of KIF14 in non - small-cell lung carcinoma and cervical carcinoma cell lines decreased proliferation and colony formation in soft agar.Conclusions: KIF14 expression is independently prognostic for disease-free survival in lung cancer and knockdown decreases tumorigenicity in vitro, showing that it is a clinically relevant oncogene and an exciting therapeutic target for further study.