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Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer
Virchows Archiv ( IF 3.4 ) Pub Date : 2020-12-09 , DOI: 10.1007/s00428-020-02983-6
M. Michl , F. Taverna , J. Kumbrink , T. S. Schiergens , V. Heinemann , J. Engel , T. Kirchner , Jens Neumann

Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of β-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high β-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns.



中文翻译:

与大肠癌转移扩散的不同模式相关的生物标志物改变

转移扩散是结直肠癌最重要的威胁生命的特征,应该主要由不同致癌途径的改变驱动。本研究比较了具有不同临床转移模式的大肠癌患者中独特生物标志物的突变和表达谱。对于病例对照研究,根据T类别,分级和原发肿瘤部位对患者进行匹配。总体上,确定了246例患有单纯肺转移(N = 82),单纯肝转移(N = 82)或非转移性结直肠癌(N = 82)的患者。检查石蜡包埋的标本中RASRAF的突变基因和β-连环蛋白和CD133的表达。临床终点为是否存在远处转移,相对于肝脏的肺转移形成及生存率。与对照组(47.6%;p = 0.04)相比,KRASNRASBRAF基因中的MAPK途径突变与肺转移的发生有关(63.4%)。MAPK途径改变和高β-catenin表达与肺转移相关,而与肝转移无关(28.0%对13.4%;p = 0.02)。与对照组相比,高CD133表达与肝转移的发生有关(30.5%对14.6%;p= 0.02)。该数据表明远距离传播的不同模式与特定的生物标志物改变有关,并且可能代表结直肠癌的不同分子亚型。然而,在不同解剖部位转移形成的潜在机制仍不清楚。由于对远距离传播的预期部位的了解将大大影响临床管理,因此需要进一步的研究以鉴定用于不同转移模式的固体生物标志物。

更新日期:2020-12-09
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