Immune-related Genes to Dominate Neutrophil-lymphocyte Ratio (NLR) Associated With Survival of Cetuximab Treatment in Metastatic Colorectal Cancer

免疫相关基因主导中性粒细胞-淋巴细胞比率 (NLR) 与转移性结直肠癌西妥昔单抗治疗的生存期相关

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作者:Yu Sunakawa, Dongyun Yang, Shu Cao, Wu Zhang, Miriana Moran, Stephanie H Astrow, Jack Hsiang, Craig Stephens, Akihito Tsuji, Takehiro Takahashi, Hiroaki Tanioka, Yuji Negoro, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Tetsuya Eto, Masashi Fujii, Wataru Ichikawa, Heinz-Josef Lenz

Background

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. Patients and

Conclusion

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.

Methods

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.

Results

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).

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