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

ABSTRACT: 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 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). 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.

SUBMITTER: Sunakawa Y

PROVIDER: S-EPMC6249067 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Sunakawa Yu Y Yang Dongyun D Cao Shu S Zhang Wu W Moran Miriana M Astrow Stephanie H SH Hsiang Jack J Stephens Craig C Tsuji Akihito A Takahashi Takehiro T Tanioka Hiroaki H Negoro Yuji Y Takagane Akinori A Tani Satoshi S Yamaguchi Tatsuro T Eto Tetsuya T Fujii Masashi M Ichikawa Wataru W Lenz Heinz-Josef HJ

Clinical colorectal cancer 20180823 4

<h4>Background</h4>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.<h4>Patients and methods</h4>In 77 patients with KRAS exon2 wild-type mCRC from prospective trials of first-line chemotherapy wit ...[more]

PMID: 30219280

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Project description:IntroductionStage IIB cervical cancer (CC) is an advanced stage CC with poor prognosis. Inflammatory response plays a crucial role in the development of CC, and systemic inflammatory indexes were related to the prognosis in several cancers. The objective of the study was to determine the prognostic value of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and systemic inflammation response index (SIRI) as inflammatory indexes in patients with stage IIB CC.Materials and methodsA retrospective study was performed in 260 patients with stage IIB CC. PLR, NLR, MLR, BLR, and SIRI were obtained from routine blood tests. Prognosis information of the patients was acquired from regular clinical follow-up. Recurrence and response to therapy were determined through electronic medical records (EMRs). Correlations of the inflammatory indexes with overall survival (OS), progression-free survival (PFS), recurrence, and response to therapy were analyzed using SPSS version 26.0 software.ResultsReceiver operating characteristic (ROC) curve analyses suggested that NLR, MLR, and SIRI had better predictive value than PLR as well as BLR in the prognosis and recurrence risk. Both univariate and multivariate survival analyses showed that higher NLR and MLR were significantly associated with shorter OS as well as PFS, whereas SIRI was not an independent predictive factor of PFS. Chi-square test results revealed that increased NLR was significantly correlated with higher recurrence rate (P=0.046), and increased MLR showed significant correlation with elevated recurrence risk (P=0.002). Univariate and binary logistic regression analyses for response to therapy indicated that elevated NLR was associated with decreased complete remission (CR) rate (P=0.031), and the P value lost statistical significance while being adjusted by tumor size (P=0.108).ConclusionsFor patients with stage IIB CC, both NLR and MLR are independent prognostic factors as well as risk factors for recurrence; NLR serves as a potential marker for therapeutic response.

Dataset Information

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

Publications

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

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