Systematically analyzed molecular characteristics of lung adenocarcinoma using metabolism-related genes classification.

High heterogeneity of lung adenocarcinoma (LUAD) is a major clinical challenge. This study aims to characterize the molecular features of LUAD through classification based on metabolism-related genes. A total of 500 LUAD samples from The Cancer Genome Atlas (TCGA) and 612 from Gene Expression Omnibus (GEO) were integrated with 2,753 metabolism-related genes to determine the molecular classification. Systematic bioinformatics analysis was used to conduct correlation analysis between metabolism-related classification and molecular characteristics of LUAD. LUAD patients were divided into three molecular clusters (C1-C3). Survival analysis revealed that C1 and C2 showed good and poor prognoses, respectively. Associational analysis of classification and molecular characteristics revealed that C1 was associated with low pathological stage, metabolic pathways, high metabolic process, active immune process and checkpoint, sensitive drug response, as well as a low genetic mutation. Nevertheless, C2 was associated with high pathological stage, carcinogenic pathways, low metabolic process, inactive immune signatures, resistant drug response, and frequent genetic mutation. Eventually, a classifier with 60 metabolic genes was constructed, confirming the robustness of molecular classification on LUAD. Our findings promote the understanding of LUAD molecular characteristics, and the research data may be used for providing information be helpful for clinical diagnosis and treatment.

LncRNA LINC00115 facilitates lung cancer progression through miR-607/ITGB1 pathway.

Dysregulated long noncoding RNAs (lncRNAs) have potential roles in various cancer types. The objective of this study was to investigate the expression and the underlying role of long intergenic nonprotein coding RNA 115 (LINC00115) in lung cancer. The relative expression of LINC00115 and miR-607 in tumor tissues and cells was detected by real-time PCR. After overexpression or knockdown of LINC00115 expression in tumor cells, the changes in the proliferation, migration, and invasion capacities were detected via Counting Kit-8 (CCK-8) assay and transwell assays. The interplay among LINC00115, miR-607, and integrin ß1 (ITGB1) was confirmed by bioinformatics analyses and luciferase reporter assay. In addition, tumor cells with LINC00115 knockdown were injected into nude mice to investigate the effect of LINC00115 on tumorigenesis in vivo. LINC00115 was highly expressed in tumor tissues and cells. LINC00115 promoted the malignant properties of tumor cells. Investigation to its molecular mechanism revealed that LINC00115 functioned as a competitive endogenous RNA (ceRNA), regulating the expression of ITGB1 by sponging miR-607 to affect tumor growth. The LINC00115/miR-607/ITGB1 signaling axis might be a novel therapeutic target in lung cancer.

Bioinformatics analysis based on DNA methylation data identified in lung adenocarcinoma subgroups with different immune characteristics and clinical outcomes.

Background: DNA methylation can be used to predict clinical outcomes and improve the classification of tumors. The present study aimed to develop a new lung adenocarcinoma (LUAD) classification system according to the immune cell gene-related methylation sites and to reveal the survival outcomes, clinical characteristics, immune cell infiltration, stem cell characteristics, and genomic variations of each molecular subgroup. Methods: The DNA methylation sites of LUAD samples collected from The Cancer Genome Atlas (TCGA) database were analyzed, and the prognosis-related differential methylation sites (DMS) were screened. Consistent clustering of the samples was conducted using ConsensusClusterPlus, and the classification results were verified by principal component analysis (PCA). The survival and clinical results, immune cell infiltration, stemness, DNA mutation, and copy number variation (CNV) of each molecular subgroup were analyzed. Results: A total of 40 DMS were obtained by difference and univariate COX analyses, and the TCGA LUAD samples were divided into three subgroups: cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Among these subgroups, the overall survival (OS) of C3 was significantly higher than that of C1 and C2. Compared with C1 and C3, C2 had the lowest innate immune cell and adaptive immune cell infiltration scores; the lowest stromal score, immune score, and iconic immune checkpoint expression; and the highest expression of messenger RNA (mRNA) expression-based stemness indices (mRNAsi), DNA methylation-based stemness index (mDNAsi), and tumor mutational burden (TMB). Conclusions: In this study, we proposed a LUAD typing system based on DMS, which was closely related to the survival, clinical features, immune characteristics, and genomic variations of LUAD, and may contribute to the development of personalized therapy for new specific subtypes.

Identification of a novel diagnosis model based on 5 hub genes for chronic thromboembolic pulmonary hypertension.

BACKGROUND: As a type of precapillary pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete pulmonary embolism resolution. In this study, we aimed to determine biomarker genes for predicting the prognosis of CTEPH. METHOD: RNAseq of CTEPH was collected from the public database, namely Gene Expression Omnibus (GEO), including GSE84538 and GSE188938, which combined a dataset (GSE). Differentially expressed genes (DEG) or miRNA (DEM) were identified by limma package. Functional enrichment analysis was performed by the WebGestaltR package. Then, the miRNA-mRNA network was presented by Cytoscape, and the protein-protein interactions (PPI) network was constructed by STRING. MCODE was mined by mature MCODE algorithm. Immune infiltration analysis was conducted by ESTIMATER and ssGSEA analysis. A diagnosis model was established by SVM algorithm. RESULT: In the GSE dataset, CTEPH samples had a lower GOBP_RESPONSE_TO_OXIDATIVE_STRESS score. A total of 628 DEGs and 31 DEMs were identified between CTEPH and normal samples. Afterward, DEGs were intersected with genes, which correlated with the GOBP_RESPONSE_TO_OXIDATIVE_STRESS score. A 26 DEMs-152 DEGs network was constructed, and a PPI network was established based on 152 DEGs to find 149 target genes. From the above 149 target genes, 3 modules were extracted to obtain 15 core targets. Finally, 5 hub genes were obtained by the intersection of 15 core targets and genes in MCODE2. A total of 5 hub genes were positively correlated with most immune cell scores as well as GOBP_RESPONSE_TO_OXIDATIVE_STRESS. It was found that a diagnosis model based on 5 hub genes had a well diagnostic ability for CTEPH. CONCLUSION: We identified 5 hub genes associated with oxidative stress. It can be concluded that they may be beneficial in diagnosing CTEPH.

Exosomal circSHKBP1 participates in non-small cell lung cancer progression through PKM2-mediated glycolysis.

Non-small cell lung cancer (NSCLC) has a high morbidity and mortality, and it is imperative to explore the latent pathogenesis mechanism of NSCLC progression to find potential prognostic biomarkers and therapeutic targets. The present study aimed to explore the biological function of circSHKBP1 in NSCLC. circSHKBP1 was found to be upregulated in NSCLC tissues and cell lines and was enriched in exosomes derived from NSCLC cells. Exosomal circSHKBP1 enhanced the proliferation, migration, invasion, and stemness of NSCLC cells. miRNA-1294 was identified as a target for circSHKBP1, and circSHKBP1 upregulated PKM2 expression by sponging miR-1294. Exosomal circSHKBP1 regulated glycolysis through PKM2 in a HIF-1α-dependent manner in NSCLC cells and promoted M2 polarization and macrophage recruitment. Moreover, exosomal circSHKBP1 promoted NSCLC cell growth, metastasis, and M2 infiltration in vivo. Thus, exosomal circSHKBP1 participated in the progression of NSCLC via the miR-1294/PKM2 axis. circSHKBP1 may be potential biomarker for the diagnosis and treatment of NSCLC.

MRI evaluation of pulmonary lesions and lung tissue changes induced by tuberculosis.

OBJECTIVE: To evaluate the utility of magnetic resonance imaging (MRI) with an advanced motion correction technique in characterizing lung tissue changes and lesions induced by pulmonary tuberculosis (TB). METHODS: Sixty-three subjects with computed tomography (CT) features of pulmonary TB underwent lung MRI. All subjects with pulmonary TB were confirmed by acid-fast bacillus (AFB) testing or the detection of Mycobacterium tuberculosis. T2-weighted turbo spin echo (TSE) sequence MRI with the MultiVane motion correction technique was used to image the lungs. Routine lung CT images were obtained as reference. MRI and CT images were reviewed by multiple readers independently. The performance of MRI in depicting abnormalities induced by pulmonary TB and their morphological changes were evaluated and compared with the performance of CT. RESULTS: Lung MRI found pulmonary abnormalities in all 63 TB subjects, with satisfactory quality. With the implementation of MultiVane for T2-weighted TSE sequences to reduce the motion correction effect, MRI showed excellent agreement with CT in detecting abnormal imaging features of pulmonary TB (κ=0.88, p<0.001), such as tree-in-bud sign, ground-glass opacity, consolidation, mass, and cavitation. MRI was advantageous in identifying caseation and liquefactive necrosis based on inhomogeneous signal distribution within consolidations and also in identifying mild pleural effusion. The optimized lung MRI was comparable to CT in detecting non-calcified nodules (κ=0.90), with overall sensitivity of 50.0%, 91.1%, and 100% for nodules of size <5 mm, 5-10 mm, and >10 mm, respectively. However, MRI was less effective in identifying lesions with calcification. CONCLUSIONS: The clinical implementation of an optimized MRI protocol with the MultiVane motion correction technique for imaging pulmonary TB is feasible. Lung MRI without ionizing radiation is a promising alternative to the clinical standard CT, especially for pregnant women, children, adolescents, and patients requiring short-term and repeated follow-up observations.