scholarly journals Integrative analysis reveals distinct subtypes with therapeutic implications in KRAS-mutant lung adenocarcinoma

EBioMedicine ◽  
2018 ◽  
Vol 36 ◽  
pp. 196-208 ◽  
Author(s):  
Ke Liu ◽  
Jintao Guo ◽  
Kuai Liu ◽  
Peiyang Fan ◽  
Yuanyuan Zeng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Integrative Analysis ◽  
Therapeutic Implications

scholarly journals PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma

2020 ◽  
Vol 12 (527) ◽  
pp. eaax3772 ◽  
Author(s):  
Xiaochao Tan ◽  
Priyam Banerjee ◽  
Edward A. Pham ◽  
Florentine U. N. Rutaganira ◽  
Kaustabh Basu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Survival ◽  
Cancer Cell ◽  
Secretory Vesicle ◽  
Effector Proteins ◽  
Therapeutic Implications ◽  
Chromosome 1Q ◽  
Biological Studies ◽  
Cancer Cell Survival ◽  
Vesicle Biogenesis

Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)–dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

Prognostic value and therapeutic implications of expanded molecular testing for resected early stage lung adenocarcinoma

Lung Cancer ◽  
2020 ◽  
Vol 143 ◽  
pp. 60-66 ◽  
Author(s):  
Peter J. Kneuertz ◽  
David P. Carbone ◽  
Desmond M. D’Souza ◽  
Konstantin Shilo ◽  
Mahmoud Abdel-Rasoul ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Early Stage ◽  
Molecular Testing ◽  
Therapeutic Implications

scholarly journals Unique MicroRNA and mRNA Interactions in EGFR-Mutated Lung Adenocarcinoma

2018 ◽  
Vol 7 (11) ◽  
pp. 419 ◽  
Author(s):  
Sophia Subat ◽  
Kentaro Inamura ◽  
Hironori Ninomiya ◽  
Hiroko Nagano ◽  
Sakae Okumura ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Regulatory Network ◽  
Egfr Mutation ◽  
Expression Profiles ◽  
Integrative Analysis ◽  
Future Research ◽  
Mutation Status ◽  
Egfr Mutated ◽  
Insight Into

The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)–mRNA interactions have been observed. However, little information is available about the miRNA–mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA–mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA–mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA–mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA–mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.

Integrative Analysis Reveals Enhanced Regulatory Effects of Human Long Intergenic Non-Coding RNAs in Lung Adenocarcinoma

2015 ◽  
Vol 42 (8) ◽  
pp. 423-436 ◽  
Author(s):  
You Zhou ◽  
Kai Wu ◽  
Jianping Jiang ◽  
Jinfei Huang ◽  
Peiwei Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Integrative Analysis ◽  
Non Coding Rnas ◽  
Regulatory Effects

scholarly journals Integrative omics analysis identifies subtypes with therapeutic implications in lung adenocarcinoma harboring KEAP1/NFE2L2

2021 ◽  
Author(s):  
Xiaodong Yang ◽  
Ming Li ◽  
Zhencong Chen ◽  
Liang Guo ◽  
Bo Jin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Mutant Cell ◽  
The Cancer Genome Atlas ◽  
Immune Microenvironment ◽  
Bioinformatics Analyses ◽  
Therapeutic Implications ◽  
Genomic Aberrations ◽  
Public Datasets

Abstract Backgrounds: Lung adenocarcinoma is one of the most common malignant tumors, in which KEAP1-NFE2L2 pathway is altered frequently. The biological features and intrinsic heterogeneities of KEAP1/NFE2L2-mutant lung adenocarcinoma remain unclear. Methods: Multiplatform data from The Cancer Genome Atlas (TCGA) were adopted to identify two subtypes of lung adenocarcinoma harboring KEAP1/NFE2L2 mutations. Bioinformatics analyses, regarding immune microenvironment, methylation level and mutational signature, were performed to characterize intrinsic heterogeneities. Meanwhile, initial results were also validated by using common lung adenocarcinoma cell lines, which revealed consistent features of KEAP1/NFE2L2-mutant subtypes. Furthermore, cell line samples were adopted for drug sensitivity screening based on public datasets. Results: Two mutant subtypes (P1 and P2) of patients were identified in TCGA. P2 patients had significantly heavier smoking levels and worse survival compared with P1 patients. The P2 subset was characterized by active immune microenvironment and more smoking-induced genomic alterations, including methylation and somatic mutations. Validations of the corresponding features in mutant cell lines were achieved to some degrees. Several compounds which were sensitive to mutant subtype of lung adenocarcinoma were identified, such as inhibitors of PI3K/Akt and IGF1R signaling pathways. Conclusions: KEAP1/NFE2L2 mutant lung adenocarcinoma showed potential heterogeneities. The intrinsic heterogeneities of KEAP1/NFE2L2 were associated with immune microenvironment and smoking-related genomic aberrations.

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