scholarly journals Role of MicroRNAs in Progression and Recurrence of Early-Stage Lung Adenocarcinoma

2015 ◽  
Vol 2 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Rama K. Singh ◽  
◽  
Drew C. Bethune ◽  
Zhaolin Xu ◽  
Susan E. Douglas ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Early Stage

scholarly journals Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zi-Hao Wang ◽  
Yu Li ◽  
Pei Zhang ◽  
Xuan Xiang ◽  
Xiao-Shan Wei ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Gene Pair ◽  
Early Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Related Gene ◽  
Tumor Immune Escape ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Infiltrating Lymphocytes

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

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.

scholarly journals CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

2021 ◽  
Author(s):  
Pedro Rocha ◽  
Ruth Salazar ◽  
Jiexin Zhang ◽  
Debora Ledesma ◽  
Jose L. Solorzano ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Critical Role ◽  
Adenocarcinoma In Situ ◽  
Invasive Adenocarcinoma ◽  
Molecular Features ◽  
Cd73 Expression

Abstract Introduction CD73 is a membrane-bound enzyme crucial in adenosine generation. The adenosinergic pathway plays a critical role in immunosuppression and in anti-tumor effects of immune checkpoint inhibitors (ICI). Here, we interrogated CD73 expression in a richly annotated cohort of human lung adenocarcinoma (LUAD) and its association with clinicopathological, immune, and molecular features to better understand the role of this immune marker in LUAD pathobiology. Materials and methods Protein expression of CD73 was evaluated by immunohistochemistry in 106 archived LUADs from patients that underwent surgical treatment without neoadjuvant therapy. Total CD73 (T +) was calculated as the average of luminal (L +) and basolateral (BL +) percentage membrane expression scores for each LUAD and was used to classify tumors into three groups based on the extent of T CD73 expression (high, low, and negative). Results CD73 expression was significantly and progressively increased across normal-appearing lung tissue, adenomatous atypical hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and LUAD. In LUAD, BL CD73 expression was associated with an increase in PD-L1 expression in tumor cells and increase of tumor-associated immune cells. Stratification of LUADs based on T CD73 extent also revealed that tumors with high expression of this enzyme overall exhibited significantly elevated immune infiltration and PD-L1 protein expression. Immune profiling demonstrated that T-cell inflammation and adenosine signatures were significantly higher in CD73-expressing lung adenocarcinomas relative to those lacking CD73. Conclusion Our study suggests that higher CD73 expression is associated with an overall augmented host immune response, suggesting potential implications in the immune pathobiology of early stage lung adenocarcinoma. Our findings warrant further studies to explore the role of CD73 in immunotherapeutic response of LUAD.

The role of Wnt pathway antagonists in early-stage lung adenocarcinoma

2021 ◽  
Author(s):  
Arife Zeybek ◽  
Necdet Öz ◽  
Serdar Kalemci ◽  
Kürşad Tosun ◽  
Tuba Gökdoğan Edgünlü ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Wnt Pathway ◽  
Early Stage

Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer

2015 ◽  
Vol 10 (2) ◽  
pp. 101-110 ◽  
Author(s):  
Matias E. Valsecchi ◽  
Gerrit Kimmey ◽  
Arvinder Bir ◽  
Damian Silbermins
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Early Stage Breast Cancer

312 The prognostic role of mesothelin expression and its association with KRAS mutation in advanced lung adenocarcinoma

2014 ◽  
Vol 50 ◽  
pp. 102
Author(s):  
A. Thomas ◽  
Y. Chen ◽  
S. Steinberg ◽  
J. Luo ◽  
G. Giaccone ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kras Mutation ◽  
Prognostic Role ◽  
Mesothelin Expression

scholarly journals The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3314
Author(s):  
Tomasz Kowalczyk ◽  
Joanna Kisluk ◽  
Karolina Pietrowska ◽  
Joanna Godzien ◽  
Miroslaw Kozlowski ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Early Stage ◽  
Chronic Obstructive ◽  
Liquid Chromatography Mass Spectrometry ◽  
Obstructive Pulmonary Disease ◽  
Cell Lung Carcinoma ◽  
Cancer Subtypes ◽  
Inflammatory State ◽  
Nsclc Patients

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

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