Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the most widely distributed tumor in the world, and its immunotherapy is not practical. Neutrophil is one of a tumor’s most abundant immune cell groups. This research aimed to investigate the complex communication network in the immune microenvironment (TIME) of NSCLC tumors to clarify the interaction between immune cells and tumors and establish a prognostic risk model that can predict immune response and prognosis of patients by analyzing the characteristics of Neutrophil differentiation. Integrated Single-cell RNA sequencing (scRNA-seq) data from NSCLC samples and Bulk RNA-seq were used for analysis. Twenty-eight main cell clusters were identified, and their interactions were clarified. Next, four subsets of Neutrophils with different differentiation states were found, closely related to immune regulation and metabolic pathways. Based on the ratio of four housekeeping genes (ACTB, GAPDH, TFRC, TUBB), six Neutrophil differentiation-related genes (NDRGs) prognostic risk models, including MS4A7, CXCR2, CSRNP1, RETN, CD177, and LUCAT1, were constructed by Elastic Net and Multivariate Cox regression, and patients’ total survival time and immunotherapy response were successfully predicted and validated in three large cohorts. Finally, the causes of the unfavorable prognosis of NSCLC caused by six prognostic genes were explored, and the small molecular compounds targeted at the anti-tumor effect of prognostic genes were screened. This study clarifies the TIME regulation network in NSCLC and emphasizes the critical role of NDRGs in predicting the prognosis of patients with NSCLC and their potential response to immunotherapy, thus providing a promising therapeutic target for NSCLC.

M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single‐cell and bulk RNA‐Seq analysis

“…40 Pang et al successfully used scRNA-seq analysis to establish a prognostic model related to neutrophils for forecasting immune responses in patients with non-small-cell lung cancer. 41 In this article, scRNAseq data of CHI3L2 in glioma were analyzed using the online TISCH2 website to seek its expressions at single cell level. We found that CHI3L2 was mainly expressed in astrocytes, endothelial cells, CD8+ T cells, mono/macrophage cells, etc.…”

“…Zhang et al also applied scRNA‐seq and bulk RNA‐seq analyses to establish a prognostic signature in ovarian cancer patients with omentum metastasis 40 . Pang et al successfully used scRNA‐seq analysis to establish a prognostic model related to neutrophils for forecasting immune responses in patients with non‐small‐cell lung cancer 41 . In this article, scRNA‐seq data of CHI3L2 in glioma were analyzed using the online TISCH2 website to seek its expressions at single cell level.…”

The double‐edged role of neutrophil heterogeneity in inflammatory diseases and cancers

“…that N2 neutrophils could release LCN2 which would in turn facilitate lung cancer metastasis. The heterogeneity of neutrophils in the peripheral blood of non‐small cell lung cancer patients were greater, and the proportion of LDNs was remarkably upregulated 305,306 . Faget et al 307 .…”

“…The heterogeneity of neutrophils in the peripheral blood of non-small cell lung cancer patients were greater, and the proportion of LDNs was remarkably upregulated. 305,306 Faget et al 307 reported that Gr1 + neutrophils could favor tumor progression by altering angiogenesis, leading to hypoxia, and sustaining Snail expression. Through METmediated nitric oxide release, neutrophils can also abate tumor growth and metastasis.…”

“…Targeting tumor‐associated CXCR2 + neutrophils and CCR2 + macrophages was reported to improve chemotherapeutic responses in pancreatic ductal adenocarcinoma 342 . In a nutshell, a series of studies have shown that it is necessary to investigate neutrophil heterogeneity in the context of pancreatic cancer treatment 266–343 . For subsequent investigation, the inductive factors of the emergence of diverse neutrophil subsets may be probed, enabling a brand‐new viewpoint for the treatment of pancreatic cancer.…”