4.6 Article

Prognostic Significance of NLR About NETosis and Lymphocytes Perturbations in Localized Renal Cell Carcinoma With Tumor Thrombus

期刊

FRONTIERS IN ONCOLOGY
卷 11, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.771545

关键词

NETosis; renal cell carcinoma; tumor thrombus; prognosis; NLR

类别

资金

  1. National Natural Science Foundation of China [82072837]
  2. Beijing Municipal Natural Science Foundation [7212083]
  3. CAMS Initiative for Innovative Medicine (CAMS-I2M) [2016-I2M-1-007]

向作者/读者索取更多资源

The study revealed that NLR is an independent risk factor for the prognosis of patients with localized RCC with tumor thrombus, and neutrophils-associated NETosis and systemic lymphocyte abnormalities are considered as markers of tumor progression in these patients.
BackgroundNon-metastatic renal cell carcinoma (RCC) with tumor thrombus showed a greater tendency for developing metastases after surgery. Early identification of patients with high risk of poor prognosis is especially important to explore adjuvant treatment of improving outcomes. Neutrophil-to-lymphocyte ratio (NLR) was a systemic inflammation marker and outcome predictor in RCC, reflecting the chaos in systemic immune status in cancer as myeloid cell expansion and lymphatic cell suppression. Neutrophil extracellular traps (NET) formation (NETosis) is the process of neutrophils generating an extracellular DNA net-like structure. NETosis in tumor was demonstrated to conduce to the subsequent metastases of tumor. However, the role of NLR for systemic immune status and tumor local immune infiltration, especially for neutrophil-associated NETs, in non-metastatic RCC with thrombus remains unclear. Patients and MethodsIn our clinical cohort, we enrolled the clinical, pathologic, and preoperative laboratory parameters of 214 RCC patients with tumor thrombus who were treated surgically. The clinical endpoint was defined as cancer-specific survival (CSS). In our basic research cohort, RNA-seq, TCR-seq, and scRNA-seq data were analyzed. Patients who reached the endpoint as recurrence-free survival (RFS) were defined as the High-risk group. Otherwise, they were separated into the Low-risk group. ResultsIn the clinical cohort, NLR >= 4 was an independent risk factor for 203 localized RCC with tumor thrombus. In the basic research cohort, tumor thrombi were separated into NETosis-thrombi belonging to the High-risk group and non-NETosis-thrombi to the Low-risk group. NETs induced by tumor-derived G-CSF in tumor thrombus has a mechanistic role in unfavorable prognosis. Besides, NETs-score from single sample GSEA (ssGSEA) algorithm was an independent prognostic factor validated in the TCGA data. Apart from the neutrophils-associated NETosis, systemic immune perturbations of lymphocytes occurred in the High-risk group, represented with decreased TCR diversity and increasingly high proportion of CD4-positive effector memory T (Tem) cells, which indirectly represented the state of lymphopenia. ConclusionsOur findings firstly demonstrated that neutrophils-associated NETosis and systemic lymphocytes perturbations were considered as tumor progression in patients of localized RCC with tumor thrombus, which reflected NLR >= 4 as an independent risk factor for patients.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据