Host MICA polymorphism as a potential predictive marker in response to chemotherapy for colorectal liver metastases
Host MICA polymorphism as a potential predictive marker in response to chemotherapy for colorectal liver metastases
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宿主 MICA 多态性作为结直肠肝转移化疗反应的潜在预测标记
DOI：
10.1159/000490411
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Inagaki Yoshinori
中科院分区：
文献类型：
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作者：
Nishioka Yujiro;Shindoh Junichi;Inagaki Yoshinori
背景：了解肿瘤的遗传背景对于更好地分层患者预后和选择最佳治疗方案非常重要。然而，对于结直肠癌肝转移（CLM），临床上可用的生物标志物仍然limited.Methods：经过全面测序的578癌症相关基因在10例患者表现出非常好/差的化疗反应，A5.1变异的theMICAgene被选为潜在的生物标志物CLM。结果：58例化疗后行CLM切除术的患者中，16例（27.6%）经直接DNA测序检测到A5.1变异，且肿瘤组织与正常肝组织中MICA变异的一致率很高（56/58，96.6%）。对38例无抗EGFR抗体治疗史的患者进行的多变量分析证实MICAA5.1与最佳CT形态学反应显著相关（OR 11.67; 95%CI 2.08-65.60;p= 0.005），并且倾向于与化疗后肿瘤存活率< 20%相关结论：MICAA5.1基因多态性与CLM切除术后化疗的CT形态学反应和复发风险降低有关。鉴于正常肝组织和CLM之间MICA变异的高一致率，宿主的遗传背景可能是CLM的新生物标志物。
Background:Understanding the genetic background of a tumor is important to better stratify patient prognosis and select optimal treatment. For colorectal liver metastases (CLM), however, clinically available biomarkers remain limited.Methods:After a comprehensive sequencing of 578 cancer-related genes in 10 patients exhibiting very good/poor responses to chemotherapy, the A5.1 variant of theMICAgene was selected as a potential biomarker for CLM. The clinical relevance ofMICAA5.1 was then investigated in 58 patients who underwent CLM resection after chemotherapy.Results:The A5.1 variant was observed in 16 (27.6%) patients examined using direct DNA sequencing, and a very high concordance rate (56/58, 96.6%) for theMICAvariant was confirmed between tumor tissues and normal liver parenchyma. A multivariate analysis of 38 patients with no history of treatment with anti-EGFR antibodies confirmed thatMICAA5.1 was significantly correlated with an optimal CT morphologic response (OR 11.67; 95% CI 2.08–65.60;p= 0.005) and tended to be correlated with a tumor viability of < 20% after chemotherapy (OR 5.91; 95% CI 0.97–36.02;p= 0.054).MICAA5.1 was also associated with a decreased risk of progression after CLM resection.Conclusion:TheMICAA5.1 polymorphism was associated with a better CT morphologic response to chemotherapy and a reduced risk of relapse after CLM resection. Given the high concordance rate inMICAvariants between normal liver tissue and CLM, the genetic background of the host could be a new biomarker for CLM.