Abstract 2265: An integrated analysis of gene mutations and gene sets for predicting paclitaxel response in lung adenocarcinoma

Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cell-free DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasma-mutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.

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Erythropoietin Receptor is a Risk Factor for Prognosis: A Potential Biomarker in Lung Adenocarcinoma

10.21203/rs.3.rs-1211017/v1 ◽

2022 ◽

Author(s):

Ya-Jing Zhang ◽

Sen-Yu Wang ◽

Song-Tao Han ◽

Yao-Yao Huang ◽

Yang-Chun Feng

Keyword(s):

Lung Adenocarcinoma ◽

Gene Mutations ◽

Predictive Ability ◽

Erythropoietin Receptor ◽

Immunohistochemical Method ◽

Normal Lung ◽

Mrna Levels ◽

Protein Levels ◽

Potential Biomarker ◽

Epor Expression

Abstract Background: Lung cancer has the highest mortality rate of all cancers, and LUAD's survival rate is particularly poor. Erythropoietin receptor (EPOR) is a member of the cytokine class I receptor family and can be detected in cancers such as lung adenocarcinoma (LUAD), however, the expression levels and prognostic value of EPOR in LUAD are still unclear.Methods: Multiple bioinformatics databases such as TIMER, Kaplan-Meier Plotter and TCGA databases, immunohistochemical method, and clinicopathological data of 92 LUADpatients between January 2008 and June 2016 were used to explore the EPOR expression, gene mutations affecting EPOR expression, EPOR-interacting or coexpressed genes, potential biological functions and the correlation of EPOR expression with prognosis, immune microenvironment and so on.All statistical analyses were performed in the R version 4.1.1.Results: In this study, the EPOR mRNA expression in LUAD tissues was possibly downregulated compared with that in normal lung tissues, but the EPOR protein expression in LUAD tissues was higher than that in paired normal lung tissues. Mutations in five genes, DDX60L, LGR6, POTEB3, RIF1 and SOX5, resulted in downregulation of EPOR expression, mutations in 10 genes includingC1orf168, DBX2 and EIF5B, resulted in upregulation of EPOR expression. Erichment analyses showed that EPOR is involved in neural tissue ligand-receptor interactions, MAPK and PI3K/Akt signaling pathways and cancer pathways. The KM Plotter and PrognoScan databases consistently concluded that EPOR was associated with prognosis in LUAD patients. Our clinicopathological data showed that high EPOR expression was associated with poorer OS (29.5 vs 46 months) and had a good predictive ability for 5-year survival probability. Conclusions: EPOR expression might be downregulated at the mRNA levels and significantly upregulated at the protein levels in LUAD, which showed that the mRNA and protein levels of EPOR are inconsistent.The high expression of EPOR was associated with poor prognosis and is expected to be a potential new prognostic marker for LUAD.

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Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese Patients

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e3182769aa8 ◽

2013 ◽

Vol 8 (1) ◽

pp. 52-61 ◽

Cited By ~ 238

Author(s):

Akihiko Yoshizawa ◽

Shinji Sumiyoshi ◽

Makoto Sonobe ◽

Masashi Kobayashi ◽

Masakazu Fujimoto ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Gene Mutations ◽

Japanese Patients ◽

Kras Gene

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Identification of a 5-Gene Metabolic Signature for Predicting Prognosis Based on an Integrated Analysis of Tumor Microenvironment in Lung Adenocarcinoma

Journal of Oncology ◽

10.1155/2020/5310793 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Xiaolin Yu ◽

Xiaomei Zhang ◽

Yanxia Zhang

Keyword(s):

Tumor Microenvironment ◽

Confidence Interval ◽

Lung Adenocarcinoma ◽

Cox Regression ◽

External Validation ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Integrated Analysis ◽

Lasso Regression ◽

The Status

Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with a depressing survival rate. The reprogramming of tumor metabolism was identified as a new hallmark of cancer in tumor microenvironment (TME), and we made a comprehensive exploration to reveal the prognostic role of the metabolic-related genes. Transcriptome profiling data of LUAD were, respectively, downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Based on the extracted metabolic-related genes, a novel 5-gene metabolic prognostic signature (including GNPNAT1, LPGAT1, TYMS, LDHA, and PTGES) was constructed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. This signature confirmed its robustness and accuracy by external validation in multiple databases. It could be an independent risk factor for LUAD, and the nomograms possessed moderately accurate performance with the C-index of 0.755 (95% confidence interval: 0.706–0.804) and 0.691 (95% confidence interval: 0.636–0.746) in training set and testing set. This signature could reveal the metabolic features according to the results of gene set enrichment analysis (GSEA) and meanwhile monitor the status of TME through ESTIMATE scores and the infiltration levels of immune cells. In conclusion, this gene signature is a cost-effective tool which could indicate the status of TME to provide more clues in the exploration of new diagnostic and therapeutic strategy.

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Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

Open Medicine ◽

10.1515/med-2016-0018 ◽

2016 ◽

Vol 11 (1) ◽

pp. 93-96 ◽

Cited By ~ 2

Author(s):

Jiang Rong ◽

Ma Chunhua ◽

Lv Yuan ◽

Mu Ning ◽

Li Jinduo ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Lung Adenocarcinoma ◽

Gene Mutation ◽

Direct Sequencing ◽

Gene Mutations ◽

Egfr Mutations ◽

Egfr Gene ◽

Sequencing Method ◽

Direct Sequencing Method ◽

Egfr Gene Mutation

AbstractObjectiveTo discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.Methods5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid.Results5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method.ConclusionARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

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