scholarly journals RBM10 Deficiency Is Associated With Increased Immune Activity in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Bing Liu ◽  
Yaqi Wang ◽  
Han Wang ◽  
Zhongwu Li ◽  
Lujing Yang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Checkpoint ◽  
Early Stage ◽  
Biological Significance ◽  
Gene Expression Signature ◽  
M2 Macrophage ◽  
Early Stage Disease ◽  
Immune Infiltration ◽  
Immune Checkpoint Molecules ◽  
Deficient Group

IntroductionRBM10 is one of the frequently mutated genes in lung adenocarcinoma (LUAD). Previous studies have confirmed that RBM10 could suppress the disease progression and cell proliferation in LUAD, but its loss-of-function mutations are more frequent in early-stage disease and decrease with the advancement of the clinical stage. This is contradictory to its role of tumor suppressor. Here, we conducted a systematic analysis to elucidate whether there was other potential biological significance of RBM10 deficiency during the progression of LUAD.Materials and MethodsThe whole exome sequencing data of 39 tumor samples from early-stage LUADs (GGN cohort) and genomic and transcriptome data of the Cancer Genome Atlas (TCGA) LUAD cohort (TCGA_LUAD cohort) and a Chinese LUAD cohort (CHOICE_ADC cohort) were first obtained. Systematic bioinformatic analyses were then conducted to determine gene expression signature, immune infiltration levels and predicted immunotherapy response. Immunohistochemistry (IHC) was also conducted to validate the result of immune infiltration.ResultsThe mutation rate of RBM10 was significantly higher in the GGN cohort than that in the TCGA_LUAD and CHOICE_ADC cohorts. In both TCGA_LUAD and CHOICE_ADC cohorts, multiple immune related pathways were markedly enriched in RBM10 deficient group. Further analyses showed that tumors with RBM10 mutations displayed higher TMB, and LUADs with RBM10 deficiency also showed higher HLA expression levels, including many HLA class I and II molecules. Additionally, many immune cells, including myeloid dendritic cells, macrophages, neutrophils and CD8+T cells, showed higher infiltration levels in LUADs with RBM10 deficiency. Finally, some immune checkpoint molecules, such as PD-L1 and TIM-3, were highly expressed in RBM10 deficient population and the predicted immunotherapy response was calculated through TIDE algorithm, showing that IFNG expression, MSI score and CD8 expression were higher in RBM10 deficient group, while MDSC and M2 macrophage were lower in RBM10 deficient group.ConclusionOur study demonstrates that RBM10 deficient LUADs show higher HLA expression and immune cell infiltration, and some immune checkpoint molecules are also highly expressed. In brief, RBM10 deficiency could enhance anti-tumor immunity in LUAD.

scholarly journals Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

2020 ◽  
Vol 13 (2) ◽  
pp. 896-903
Author(s):  
Brendan Seng Hup Chia ◽  
Wen Long Nei ◽  
Sabanayagam Charumathi ◽  
Kam Weng Fong ◽  
Min-Han Tan
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Disease ◽  
Lung Cancer Patients ◽  
Limited Stage ◽  
Potential Biomarker ◽  
Egfr Mutant

The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13.5 months, an association between a detectable pre-radiotherapy plasma EGFR ctDNA and early tumour relapse (155 days vs. NR, p = 0.004) was noted. One patient with persistent plasma EGFR ctDNA predated radiological progression. The role of ctDNA in early-stage lung cancer is developing. Plasma EGFR ctDNA could be a useful biomarker in lung cancer patients undergoing radical treatments for staging, prognostication, and follow-up. These preliminary findings should be explored in larger studies.

scholarly journals A robust prognostic gene expression signature for early stage lung adenocarcinoma

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Marcin Krzystanek ◽  
Judit Moldvay ◽  
David Szüts ◽  
Zoltan Szallasi ◽  
Aron Charles Eklund
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Gene Expression Signature ◽  
Expression Signature ◽  
Prognostic Gene

scholarly journals Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

2020 ◽  
Vol 6 (4) ◽  
pp. 48
Author(s):  
Elisa Dama ◽  
Valentina Melocchi ◽  
Francesco Mazzarelli ◽  
Tommaso Colangelo ◽  
Roberto Cuttano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Regulatory Networks ◽  
Early Stage ◽  
Stage I ◽  
Prognostic Biomarkers ◽  
Early Stage Disease ◽  
Ct Screening ◽  
Lung Cancer Patients ◽  
Reduction Of Mortality

Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine.

BRAF kinase in melanoma development and progression

2008 ◽  
Vol 10 ◽  
Author(s):  
Amena M. DeLuca ◽  
Archana Srinivas ◽  
Rhoda M. Alani
Keyword(s):  
Large Scale ◽  
Early Stage ◽  
Biological Significance ◽  
Average Life Expectancy ◽  
Kinase Gene ◽  
Early Stage Disease ◽  
Molecular Alterations ◽  
Activating Mutations ◽  
Stage Disease ◽  
The Usa

Cutaneous melanoma is increasing in incidence at one of the highest rates for any form of cancer in the USA, with a current lifetime incidence of 1 in 68. Although early-stage disease is often curable, the survival rate for advanced disease is low, with an average life expectancy of 6–10 months. Knowledge of the molecular alterations associated with melanoma development and progression is expected to lead to improved therapies and outcomes. Major progress in defining the molecular alterations associated with the evolution of melanoma came in 2002, through a systematic genome-wide assessment of cancer-associated pathways. Large-scale sequencing of growth-associated genes in a variety of cancers identified a high frequency (>60%) of activating mutations of the BRAF kinase gene in human melanomas. This discovery has prompted a large number of studies evaluating the biological significance of BRAF kinase mutations in the initiation and progression of melanoma, and their importance for the development of novel melanoma therapies. Here we review the most recent studies of BRAF kinase in the pathogenesis of melanoma and their implications for defining BRAF kinase as a therapeutic point of interest in melanoma.

scholarly journals Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers

2021 ◽  
Author(s):  
Mark A. Baxter ◽  
Fearghas Middleton ◽  
Hannah P. Cagney ◽  
Russell D. Petty
Keyword(s):  
Oesophageal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Patient Specific ◽  
Cancer Type ◽  
Early Stage Disease ◽  
Treatment Paradigm ◽  
Research Challenge

AbstractImmune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing. Unfortunately, however, ICI-responding patients appear to constitute a minority subgroup within gastro-oesophageal cancer, and resistance to ICI therapy (whether primary or acquired) is common. Understanding the biological mechanisms of ICI resistance is a current major research challenge and involves investigation of both tumour and patient-specific factors. In this review, we discuss the mechanisms underlying ICI resistance and their potential specific applications of this knowledge towards precision medicine strategies in the management of gastro-oesophageal cancers in clinical practice.

scholarly journals Comprehensive Analysis of Clinical Significance, Immune Infiltration and Biological Role of m6A Regulators in Early-Stage Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Bolun Zhou ◽  
Shugeng Gao
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Adoptive T Cell Therapy ◽  
Predictive Score ◽  
Poor Overall Survival ◽  
T Cell Therapy ◽  
Immune Infiltration ◽  
Mutation Burden

Recent publications have revealed that N6-methyladenosine (m6A) modification is critically involved in tumorigenesis and metastasis. However, the correlation of m6A modification and immune infiltration in early-stage lung adenocarcinoma (LUAD) is still uncertain. We performed NMF clustering based on 23 m6A regulators and identify three distinct m6A clusters and three m6A related genes clusters (m6A cluster-R) in early-stage LUAD. The immune infiltrating levels were calculated using CIBERSORT, MCPcounter and ssGSEA algorithms. And we established the m6A-predictive score to quantify m6A modified phenotypes and predict immunotherapeutic responses. Based on the TME characteristics, different immune profiles were also identified among three m6A gene-related clusters. And the m6A-R-C2 was related to a favorable overall survival (OS), whereas m6A-R-C3 had unfavorable overall survival. The m6A-predictive score was built according to the expression levels of m6A-related genes, and patients could be stratified into subgroups with low/high scores. Patients with high scores had poor overall survival, enhanced immune infiltration, high tumor mutation burden and increased level of somatic mutation. Besides, patients with high scores had unfavorable overall survival in the anti-PD-1 cohort, whereas the overall survival of high-score patients was better in the adoptive T cell therapy cohort. Our work highlights that m6A modification is closely related to immune infiltration in early-stage LUAD, which also contributes to the development of more effective immunotherapy strategies.

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