Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer.
Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer.
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DOI：
10.1038/bjc.2013.197
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发表时间：
2013-05-28
影响因子：
8.8
通讯作者：
Lugli A
中科院分区：
文献类型：
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作者：
Koelzer VH;Karamitopoulou E;Dawson H;Kondi-Pafiti A;Zlobec I;Lugli A
本研究探讨Raf-1Kinase Inhibitor Protein(RKIP)在结直肠癌(CRC)中的地理表达模式及其与临床病理、分子生物学特征、上皮-间充质转化(EMT)标志物及预后的关系。对220例特征良好的癌组织切片进行RKIP免疫组织化学染色。使用匹配的多冲孔组织芯片评估核因子-κB和E-钙粘附素的表达。分析错配修复(MMR)蛋白表达、B-Raf和KRAS突变情况。RKIP在正常粘膜、肿瘤中心、侵袭前沿和肿瘤芽中的表达均被评估为临床相关性。RKIP在正常粘膜中呈弥漫性表达，向肿瘤中心和肿瘤前部逐渐消失(P<；0.0001)。只有0.9%的肿瘤芽呈RKIP阳性。在肿瘤中心，RKIP缺乏预示着转移性疾病(P=0.0307)、血管侵犯(P=0.0506)、肿瘤萌芽(P=0.0112)和侵袭性边界形态(P=0.0084)。RKIP缺失与核因子-κB活化(P=0.0002)和E-钙粘附素缺失(P<；0.0001)相关。RKIP缺失在MMR缺陷型癌症中更为常见(P=0.0191)，而未观察到KRAS和B-Raf突变的影响。肿瘤中心的RKIP是一个独立于肿瘤分期和治疗的预后指标(HR(95%CI)：2.13(1.27~3.56；P=0.0042))。RKIP表达作为独立预后因素的临床相关性仅限于肿瘤中心。RKIP的缺失可以预测EMT的特征，并与频繁的远处转移相关。
This study evaluates the geographic expression pattern of Raf-1 Kinase Inhibitor Protein (RKIP) in colorectal cancer (CRC) in correlation with clinicopathological and molecular features, markers of epithelial-mesenchymal transition (EMT) and survival outcome. Whole-tissue sections of 220 well-characterised CRCs were immunostained for RKIP. NF-κB and E-Cadherin expression was assessed using a matched multi-punch tissue microarray. Analysis of mismatch repair (MMR) protein expression, B-Raf and KRAS mutations was performed. RKIP expression in normal mucosa, tumour centre, invasion front and tumour buds was each assessed for clinical relevance. RKIP was diffusely expressed in normal mucosa and progressively lost towards tumour centre and front (P<0.0001). Only 0.9% of tumour buds were RKIP-positive. In the tumour centre, RKIP deficiency predicted metastatic disease (P=0.0307), vascular invasion (P=0.0506), tumour budding (P=0.0112) and an invasive border configuration (P=0.0084). Loss of RKIP correlated with NF-κB activation (P=0.0002) and loss of E-Cadherin (P<0.0001). Absence of RKIP was more common in MMR-deficient cancers (P=0.0191), while no impact of KRAS and B-Raf mutation was observed. RKIP in the tumour centre was identified as a strong prognostic indicator (HR (95% CI): 2.13 (1.27–3.56); P=0.0042) independently of TNM classification and therapy (P=0.0474). The clinical relevance of RKIP expression as an independent prognostic factor is restricted to the tumour centre. Loss of RKIP predicts features of EMT and correlates with frequent distant metastasis.
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影响因子：
3.4
作者：
Koelzer, Viktor Hendrik;Baker, Kristi;Zlobec, Inti
通讯作者：
Zlobec, Inti
影响因子：
11.2
作者：
Al-Mulla, Fahd;Bitar, Milad S.;Kolch, Walter
通讯作者：
Kolch, Walter
DOI：
10.1186/1756-9966-31-30
发表时间：
2012-03-31
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
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作者：
Fujimori Y;Inokuchi M;Takagi Y;Kato K;Kojima K;Sugihara K
通讯作者：
Sugihara K
影响因子：
2.8
作者：
Kim, Hyun-Soo;Won, Kyu Yeoun;Kim, Youn Wha
通讯作者：
Kim, Youn Wha
影响因子：
8.8
作者：
通讯作者：
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