ObjectivesDerived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs.DesignThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesPubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020.Eligibility criteria(1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves.Data extraction and synthesisTwo investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran’s Q test and I2 statistics. Publication bias of studies was assessed by Begg’s test and Egger’s test. We used V.12.0 of the Stata statistical software.ResultsThis analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg’s test and Egger’s linear regression test.ConclusionsThis meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings.PROSPERO registration numberCRD42021214034.

Background The immunological tumour microenvironment (TME) has occupied a very important position in the beginning and progression of non-small cell lung cancer (NSCLC). Prognosis of lung adenocarcinoma (LUAD) remains poor for the local progression and widely metastases at the time of clinical diagnosis. Our objective is to identify a potential signature model to improve prognosis of LUAD. Methods With the aim to identify a novel immune prognostic signature associated with overall survival (OS), we analysed LUADs extracted from The Cancer Genome Atlas (TCGA). Immune scores and stromal scores of TCGA-LUAD were downloaded from Estimation of STromal and Immune cells in MAlignant Tumour tissues Expression using data (ESTIMATE). LASSO COX regression was applied to build the prediction model. Then, the prognostic gene signature was validated in the GSE68465 dataset. Results The data from TCGA datasets showed patients in stage I and stage II had higher stromal scores than patients in stage IV (P < 0.05), and for immune score patients in stage I were higher than patients in stage III and stage IV (P < 0.05). The improved overall survivals were observed in high stromal score and immune score groups. Patients in the high-risk group exhibited the inferior OS (P = 2.501e − 05). By validating the 397 LUAD patients from GSE68465, we observed a better OS in the low-risk group compared to the high-risk group, which is consistent with the results from the TCGA cohort. Nomogram results showed that practical and predicted survival coincided very well, especially for 3-year survival. Conclusion We obtained an 11 immune score related gene signature model as an independent element to effectively classify LUADs into different risk groups, which might provide a support for precision treatments. Moreover, immune score may play a potential valuable sole for estimating OS in LUADs.

Background: Cancer poses a serious threat to human health. Clarifying the potential significance of Bruton's tyrosine kinase (BTK)in cancer has potential clinical value. This study examined the prognostic and immunological value of BTK gene expression in pan-cancer.Methods: We evaluated the gene expression of BTK in tumor tissues and normal tissues in different cancers. Survival analysis, including Kaplan–Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s method was conducted to analyze the interrelation between BTK gene expression and tumor mutational burden (TMB)and microsatellite instability (MSI). We explored the association of BTK expression with the tumor microenvironment based on Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Co-expression analysis of BTK expression and immune-related genes was performed. We used Gene Set Enrichment Analysis (GSEA) to examine the molecular mechanisms and pathways of BTK in pan-cancer.Results: High BTK expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) was positively correlated with patient prognosis, while high expression of BTK in lymphoid neoplasm diffuse large B cell lymphoma (DLBC), brain lower grade glioma (LGG) and esophageal carcinoma (ESCA) corresponded with a worse prognosis. Cox analysis showed that BTK was closely associated to the prognosis of HNSC, LGG, SKCM and LUAD. BTK expression was correlated with clinical stage, TMB and MSI of 10 types of tumors. In HNSC, LGG, LUAD and SKCM, the expression of BTK was positive correlated with immune and stromal scores. Conclusion: BTK expression can act as a prognostic factor in various cancers, especially in HNSC, LGG, LUAD and SKCM, and this may be from its close association with TMB, MSI and immune cell infiltration.

Bruton's tyrosine kinase (BTK), a key B-cell and macrophage kinase, plays a pivotal role in oncogenic pathways in many B-cell malignancies. BTK inhibitors have shown promising anti-tumor activity, first in B-cell malignancies and subsequently in other tumors. However, the prognostic role of BTK in human tumors remains largely unexplored. In this study, we aim to explore the prognostic value of BTK expression in 33 human tumors using pan-cancer analyses. Survival analyses, including Kaplan-Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s correlation analysis was conducted to determine the interrelations between BTK and tumor mutational burden (TMB) and between BTK and microsatellite instability (MSI). The Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data (ESTIMATE) algorithm was used to explore the association of BTK with the tumor microenvironment and Gene Set Enrichment Analysis (GSEA) was used to examine the underlying mechanisms of BTK’s role in multiple tumors. BTK expression is closely associated with the prognosis of head and neck squamous cell carcinoma (HNSC), brain lower grade glioma (LGG), skin cutaneous melanoma (SKCM), and lung adenocarcinoma (LUAD). BTK expression was correlated with clinical stage, TMB, and MSI in 10 types of tumors. In HNSC, LGG, LUAD, and SKCM, BTK expression was positively correlated with immune and stromal scores. BTK is a prognostic biomarker in multiple tumors, especially in HNSC, LGG, LUAD, and SKCM, and this is closely associated with tumor microenvironment remodeling.