Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
Clin Colorectal Cancer. 2018 Dec;17(4):e741-e749. doi: 10.1016/j.clcc.2018.08.002. Epub 2018 Aug 23.
Few clinical studies have investigated the association between neutrophil-lymphocyte ratio (NLR) and treatment with cetuximab-based chemotherapy in metastatic colorectal cancer (mCRC). The NLR may reflect immune cells modulating specific cytokine signals in the tumor microenvironment; however, which immune-related genes affect the NLR remain unclear.
In 77 patients with KRAS exon2 wild-type mCRC from prospective trials of first-line chemotherapy with cetuximab, expression levels of 354 immune-related genes were measured in tissue samples obtained from all patients by the HTG EdgeSeq Oncology Biomarker Panel. The association between the NLR and clinical outcomes was evaluated using the Spearman rank correlation coefficient. In addition, 2-sample t tests were performed to investigate which genes among the top 100 genes associated with survival had significantly different expression levels between the NLR-low and NLR-high groups among all measured genes.
NLR data were available for 71 patients. The NLR was associated with progression-free survival and overall survival (r = -0.24; P = .040 and r = -0.29; P = .010, respectively). When stratified by the median value of the NLR, the Kaplan-Meier curve of NLR-low versus NLR-high differed significantly for both progression-free survival (median, 11.8 vs. 9.1 months; P = .036) and overall survival (median, 42.8 vs. 26.7 months; P = .029). The 2-sample t test revealed that the expression levels of the LYZ, TYMP, and CD68 genes differed significantly between the NLR-low and NLR-high groups (t test P-value < .005; false discovery rate P-value < .15).
NLR is significantly associated with survival in patients with mCRC treated with first-line chemotherapy with cetuximab. Genes encoding for activities on macrophages may affect the NLR.
鲜有临床研究调查中性粒细胞与淋巴细胞比值（NLR）与转移性结直肠癌（mCRC）患者接受西妥昔单抗为基础的化疗之间的关系。NLR 可能反映了免疫细胞在肿瘤微环境中调节特定细胞因子信号；然而，哪些免疫相关基因影响 NLR 尚不清楚。
在来自前瞻性试验的 77 例 KRAS 外显子 2 野生型 mCRC 患者中，通过 HTG EdgeSeq 肿瘤生物标志物面板检测所有患者组织样本中 354 个免疫相关基因的表达水平。采用 Spearman 秩相关系数评估 NLR 与临床结局的关系。此外，采用两样本 t 检验研究在所有测量基因中与生存相关的前 100 个基因中哪些基因的表达水平在 NLR 低与 NLR 高组之间存在显著差异。
NLR 数据可用于 71 例患者。NLR 与无进展生存期和总生存期相关（r=-0.24；P=0.040 和 r=-0.29；P=0.010）。按 NLR 中位数进行分层时，NLR 低与 NLR 高组的无进展生存（中位值：11.8 与 9.1 个月；P=0.036）和总生存（中位值：42.8 与 26.7 个月；P=0.029）的 Kaplan-Meier 曲线差异有统计学意义。两样本 t 检验显示，LYZ、TYMP 和 CD68 基因的表达水平在 NLR 低与 NLR 高组之间存在显著差异（t 检验 P 值<0.005；错误发现率 P 值<0.15）。
NLR 与接受西妥昔单抗为基础的一线化疗的 mCRC 患者的生存显著相关。编码巨噬细胞活性的基因可能影响 NLR。
