Immune subgroup analysis for non-small cell lung cancer may be a good choice for evaluating therapeutic efficacy and prognosis.
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ABSTRACT:
SUBMITTER: Tian Y
PROVIDER: S-EPMC8148502 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Neuroendcrine carcinoma (NEC) of lung consists of small-cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Although long-term outcomes of SCLC patients are usually poor, a few patients achieve long-term survivals. Prognostic factors in SCLC have not been fully elucidated. microRNAs (miRNAs) are known to negatively regulate gene expression and to be relevant to tumorigenesis, tumor classification and prognosis. Methods 63 samples (46 neuroendocrine carcinoma including 35 SCLC and 11 LCNEC, 4 adenocarcinoma, 5 squamous cell carcinoma and 8 normal lung) were obtained through surgical resection. miRNA expression in each sample was comprehensively investigated using miRNA microarray. Results Unsupervised hierarchial clustering classified the all NEC into two subgroups, group 1 and 2. Group 1 was felt into an independent branch that consisted of only NEC, whereas group 2 was included in a branch that contained both NEC and non-NEC. Compared with SCLC of group 1 (SCLC 1), SCLC of group 2 (SCLC 2) was a distinct subgroup with surprisingly good prognosis (0% v 79% survived for 5 years; p=0.007). Serum proGRP level was significantly lower in SCLC 2 than in SCLC 1 despite of similar tumor stages between the two groups. Among 12 cases treated by presurgical chemotherapy, PR:NC ratio was 6:3 in SCLC 1 and 2:1 in SCLC 2, suggesting no apparent difference of chemosensitivity. Histologically, distinction between both groups was difficult. Cox regression analysis demonstrated that three miRNA signature was correlated with survival of SCLC patients. These prognostic miRNAs were differentially expressed between SCLC 1 and 2, which were validated by quantitative real time RT-PCR. Bioinformatics analysis predicted that these miRNAs targeted not only genes involving with tumorigenesis but also genes associated with neuroendocrine function. Conclusion miRNA expression profiling identified a distinct subgroup of SCLC with favorable prognosis. This subgroup might have less neuroendocrine character than usual SCLC. All samples were tissue samples obtained by surgical resection. 35 samples of small-cell lung cancer were investigated. 11 samples of larege cell neuroendocrine cancer, 4 samples of adenocarcinoma, 5 samples of squamous cell carcinoma and 8 samples of normal lung were also included as reference.
| S-ECPF-GEOD-19945 | biostudies-other
Project description:Background Neuroendcrine carcinoma (NEC) of lung consists of small-cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Although long-term outcomes of SCLC patients are usually poor, a few patients achieve long-term survivals. Prognostic factors in SCLC have not been fully elucidated. microRNAs (miRNAs) are known to negatively regulate gene expression and to be relevant to tumorigenesis, tumor classification and prognosis. Methods 63 samples (46 neuroendocrine carcinoma including 35 SCLC and 11 LCNEC, 4 adenocarcinoma, 5 squamous cell carcinoma and 8 normal lung) were obtained through surgical resection. miRNA expression in each sample was comprehensively investigated using miRNA microarray. Results Unsupervised hierarchial clustering classified the all NEC into two subgroups, group 1 and 2. Group 1 was felt into an independent branch that consisted of only NEC, whereas group 2 was included in a branch that contained both NEC and non-NEC. Compared with SCLC of group 1 (SCLC 1), SCLC of group 2 (SCLC 2) was a distinct subgroup with surprisingly good prognosis (0% v 79% survived for 5 years; p=0.007). Serum proGRP level was significantly lower in SCLC 2 than in SCLC 1 despite of similar tumor stages between the two groups. Among 12 cases treated by presurgical chemotherapy, PR:NC ratio was 6:3 in SCLC 1 and 2:1 in SCLC 2, suggesting no apparent difference of chemosensitivity. Histologically, distinction between both groups was difficult. Cox regression analysis demonstrated that three miRNA signature was correlated with survival of SCLC patients. These prognostic miRNAs were differentially expressed between SCLC 1 and 2, which were validated by quantitative real time RT-PCR. Bioinformatics analysis predicted that these miRNAs targeted not only genes involving with tumorigenesis but also genes associated with neuroendocrine function. Conclusion miRNA expression profiling identified a distinct subgroup of SCLC with favorable prognosis. This subgroup might have less neuroendocrine character than usual SCLC. All samples were tissue samples obtained by surgical resection. 35 samples of small-cell lung cancer were investigated. 11 samples of larege cell neuroendocrine cancer, 4 samples of adenocarcinoma, 5 samples of squamous cell carcinoma and 8 samples of normal lung were also included as reference.
2013-01-31 | E-GEOD-19945 | biostudies-arrayexpress
Project description:Background Neuroendcrine carcinoma (NEC) of lung consists of small-cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Although long-term outcomes of SCLC patients are usually poor, a few patients achieve long-term survivals. Prognostic factors in SCLC have not been fully elucidated. microRNAs (miRNAs) are known to negatively regulate gene expression and to be relevant to tumorigenesis, tumor classification and prognosis. Methods 63 samples (46 neuroendocrine carcinoma including 35 SCLC and 11 LCNEC, 4 adenocarcinoma, 5 squamous cell carcinoma and 8 normal lung) were obtained through surgical resection. miRNA expression in each sample was comprehensively investigated using miRNA microarray. Results Unsupervised hierarchial clustering classified the all NEC into two subgroups, group 1 and 2. Group 1 was felt into an independent branch that consisted of only NEC, whereas group 2 was included in a branch that contained both NEC and non-NEC. Compared with SCLC of group 1 (SCLC 1), SCLC of group 2 (SCLC 2) was a distinct subgroup with surprisingly good prognosis (0% v 79% survived for 5 years; p=0.007). Serum proGRP level was significantly lower in SCLC 2 than in SCLC 1 despite of similar tumor stages between the two groups. Among 12 cases treated by presurgical chemotherapy, PR:NC ratio was 6:3 in SCLC 1 and 2:1 in SCLC 2, suggesting no apparent difference of chemosensitivity. Histologically, distinction between both groups was difficult. Cox regression analysis demonstrated that three miRNA signature was correlated with survival of SCLC patients. These prognostic miRNAs were differentially expressed between SCLC 1 and 2, which were validated by quantitative real time RT-PCR. Bioinformatics analysis predicted that these miRNAs targeted not only genes involving with tumorigenesis but also genes associated with neuroendocrine function. Conclusion miRNA expression profiling identified a distinct subgroup of SCLC with favorable prognosis. This subgroup might have less neuroendocrine character than usual SCLC.
2013-01-31 | GSE19945 | GEO
Project description:This paper examines how to maximize contribution in public good dilemmas by arranging people into homogeneous or heterogeneous subgroups. Past studies on the effect of homogeneity of efficacy have exclusively manipulated group composition in their experimental designs, which might have imposed a limit on ecological validity because group membership may not be easily changed in reality. In this study, we maintained the same group composition but varied the subgroup composition. We developed a public good dilemmas paradigm in which participants were assigned to one of the four conditions (high- vs. low-efficacy; homogeneous vs. heterogeneous subgroup) to produce their endowments and then to decide how much to contribute. We found that individuals in homogeneous and heterogeneous subgroups produced a similar amount and proportion of contribution, which was due to the two mediating effects that counteracted each other, namely (a) perceived efficacy relative to subgroup and (b) expectation of contribution of other subgroup members. This paper demonstrates both the pros and cons of arranging people into homogeneous and heterogeneous subgroups of efficacy.
| S-EPMC6067760 | biostudies-literature
Project description:A primary factor in tumor morbidity and mortality, lung adenocarcinoma (LUAD) is known to be a major subtype of lung cancer, having the lowest survival rate among all other cancers. Using The Cancer Genome Atlas (TCGA) database the relationship between the immune infiltrate and the NUP62CL was explored and the value of the NUP62CL expression in the prognosis and diagnosis LUAD was examined. Using the logistic regression and the Wilcoxon signed-rank test the relationship between the NUP62CL and the clinico-pathological features was analyzed. There was a significant correlation between the clinical stage (p = 0.005), the N (p = 0.004), and the decreased expression of NUP62CL. The prognosis of LUAD with high NUP62CL expression was revealed to be worse than that with low NUP62CL expression (p < 0.001) by the Kaplan-Meier survival analysis. The potentiality of NUP62CL to be a significant factor of prognosis for LUAD was indicated by the analyses of the multivariate and the univariate Cox regression models. In LUAD, the crucial role of recombination and maintenance of telomere as a significant pathway for NUP62CL was suggested by the Gene Set Enrichment Analysis (GSEA). To analyze the correlation between the genes and the tumor infiltrating immune cells the CIBERSORT was used. Moreover the positive correlation with the NUP62CL expression in LUAD of the infiltration level of the tumor infiltrating B lymphocytes and memory CD4+ T cells was exhibited by CIBERSORT. Therefore, NUP62CL may be a new valuable prognostic indicator for LUAD.
| S-EPMC8124116 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) are new therapeutic strategies for non-small cell lung cancer (NSCLC). We aimed to quantitatively evaluate the efficacy and safety of ICIs in NSCLC. Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized clinical trials comparing ICIs with control therapies in NSCLC. Data were pooled according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A total of 12 trails comprising 6,919 NSCLC patients were included in this meta-analysis. ICIs therapies significantly improved progression-free survival (PFS) (HR, 0.838; P < 0.001), overall survival (OS) (HR, 0.747; P < 0.001) and objective response rates (ORR) (RR, 1.311; P < 0.001) in NSCLC. Prognostic benefit was observed irrespective of age, sex, treatment line, performance status and histology. Survival improvement of ICIs was limited for NSCLC patients with non-smoker (PFS, P = 0.468; OS, P = 0.317) or central nervous system (CNS) metastasis (PFS, P = 0.209; OS, P = 0.090), or positive EGFR mutation (PFS, P = 0.083; OS, P = 0.522) or PD-L1 expression level less than 5% (PFS, P = 0.370; OS, P = 0.047). The relative risks of all-grade and high-grade (≥3) anemia, neutropenia, leukopenia, thrombocytopenia, stomatitis, nausea, pyrexia, asthenia and neuropathy were all decreased in patients received ICIs compared with control therapies. This meta-analysis provides clinical evidence that ICIs improve PFS, OS, and ORR in NSCLC with fewer adverse effects. Our data establish ICIs as a prefer treatment option for NSCLC patients with smoker, no CNS metastasis, wild type EGFR, and high PD-L1 expression.
| S-EPMC6136858 | biostudies-other
Project description: Not available
| S-EPMC9552090 | biostudies-literature
Project description:The EphA family belongs to a large group of membrane receptor tyrosine kinases. Emerging evidence indicates that the EphA family participates in tumour occurrence and progression. Nonetheless, the expression patterns and prognostic values of the nine EphAs in non-small cell lung cancer (NSCLC) have rarely been studied before. In the current study, we comprehensively analysed the expression and prognostic role of EphA family members by different means. The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases were used to investigate the expression of EphAs in NSCLC. The cBioPortal database was applied to analyse the prognostic values and genetic mutations of EphAs.We discovered that the expression of EphA10 was significantly higher in NSCLC tissues than in adjacent noncancerous tissues, and survival analyses showed that a higher level of EphA10 predicted poor prognosis. Further exploration into the role of EphA10 by ESTIMATE, CIBERSORT, and ssGSEA analysis found that it was also related to immune infiltration and higher expression of targets of ICI targets. In conclusion, this study revealed that among the EphA family members, EphA10 played an oncogenic role and was a promising biomarker for poor prognosis and better immunotherapy response in NSCLC.
| S-EPMC11344161 | biostudies-literature
Project description:BackgroundsThe high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved.MethodsUsing R software, we performed Kaplan-Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis.ResultsOn the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6.ConclusionB cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.
| S-EPMC8370893 | biostudies-literature
Project description:BackgroundFollicular lymphoma (FL) prognosis is influenced by the composition of the tumour microenvironment. We tested an automated approach to quantitatively assess the phenotypic and spatial immune infiltrate diversity as a prognostic biomarker for FL patients.MethodsDiagnostic biopsies were collected from 127 FL patients initially treated with rituximab-based therapy (52%), radiotherapy (28%), or active surveillance (20%). Tissue microarrays were constructed and stained using multiplex immunofluorescence (CD4, CD8, FOXP3, CD21, PD-1, CD68, and DAPI). Subsequently, sections underwent automated cell scoring and analysis of spatial interactions, defined as cells co-occurring within 30 μm. Shannon's entropy, a metric describing species biodiversity in ecological habitats, was applied to quantify immune infiltrate diversity of cell types and spatial interactions. Immune infiltrate diversity indices were tested in multivariable Cox regression and Kaplan-Meier analysis for overall (OS) and progression-free survival (PFS).ResultsIncreased diversity of cell types (HR = 0.19 95% CI 0.06-0.65, p = 0.008) and cell spatial interactions (HR = 0.39, 95% CI 0.20-0.75, p = 0.005) was associated with favourable OS, independent of the Follicular Lymphoma International Prognostic Index. In the rituximab-treated subset, the favourable trend between diversity and PFS did not reach statistical significance.ConclusionMultiplex immunofluorescence and Shannon's entropy can objectively quantify immune infiltrate diversity and generate prognostic information in FL. This automated approach warrants validation in additional FL cohorts, and its applicability as a pre-treatment biomarker to identify high-risk patients should be further explored. The multiplex image dataset generated by this study is shared publicly to encourage further research on the FL microenvironment.
| S-EPMC8571143 | biostudies-literature