Santos Marisa D, Silva Cristina, Rocha Anabela, Nogueira Carlos, Castro-Poças Fernando, Araujo António, Matos Eduarda, Pereira Carina, Medeiros Rui, Lopes Carlos
Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal.
Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.
Oncotarget. 2017 Jul 28;8(35):58133-58151. doi: 10.18632/oncotarget.19651. eCollection 2017 Aug 29.
Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: "good responders" (Mandard TRG1-2) and "poor responders" (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in gene maintain predictive value, allowing a clinical model design.
It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.
只有出现病理反应,新辅助放化疗(nCRT)治疗的直肠癌患者生存率才会提高。曼德尔肿瘤退缩分级(TRG)被证明是衡量nCRT反应的有效系统。治疗前预测肿瘤反应的能力可能会显著影响直肠癌患者nCRT的选择。目的是确定曼德尔反应的潜在预测性预处理因素,并构建一个临床预测模型设计。167例局部晚期直肠癌患者接受了nCRT和根治性手术。分析外周血血细胞计数。评估预处理活检中环蛋白D1、表皮生长因子受体(EGFR)、血管内皮生长因子(VEGF)和蛋白21的表达。通过多重扩增后进行质谱产物分离,使用Sequenom平台对总共61个单核苷酸多态性进行了特征分析。手术标本根据曼德尔TRG进行分类。患者分为:“良好反应者”(曼德尔TRG1 - 2)和“不良反应者”(曼德尔TGR3 - 5)。我们检查了曼德尔反应的预测因素并进行了统计分析。在单变量分析中,距肛缘距离、中性粒细胞淋巴细胞比值(NLR)、环蛋白D1、VEGF、EGFR、蛋白21和rs1810871白细胞介素10基因多态性是对曼德尔反应具有预测价值的预处理变量。在多变量分析中,NLR、环蛋白D1、蛋白21和基因中的rs1800871保持预测价值,从而可以进行临床模型设计。
似乎可以利用血液和组织生物标志物的预处理表达,构建直肠癌新辅助放化疗肿瘤反应预测模型。