LINC00324 affects non-small cell lung cancer cell proliferation and invasion through regulation of the miR-139-5p/IGF1R axis.

Long non-coding RNAs (lncRNAs) are proved to perform critical function in regulating cancer cell behavior. It is reported that LINC00324 promotes lung adenocarcinoma development by regulating miR-615-5p/AKT1 axis. This study aimed to demonstrate whether LINC00324 participates in non-small cell lung cancer (NSCLC) pathogenesis through other molecular mechanism. Relative mRNA, lncRNA, and microRNA levels were analyzed using quantitative real-time-polymerase chain reaction (qRT-PCR). Western blot was used to detect protein level. MTT assay shown proliferation ability and transwell assay shown invasive ability. Luciferase reporter assay illustrated the interaction between RNA molecules. In NSCLC, the high expression of LINC00324 had correlation with the poor prognosis. LINC00324 promoted the proliferation and invasion of NSCLC cells while miR-139-5p inhibited these behaviors. LINC00324 overexpression promoted insulin-like growth factor 1 receptor (IGF1R) expression via absorbing miR-139-5p. The tumor-promoting effects of LINC00324 were attenuated through miR-139-5p overexpression. Highly expressed LINC00324 in NSCLC through sponged miR-139-5p to elevate IGF1R expression and promoted cell proliferation and invasion. This research demonstrated that LINC00324 is a potential NSCLC diagnosis and therapy target.

Esophageal reconstruction: posterior mediastinal or retrosternal route.

BACKGROUND: Although posterior mediastinal (PM) route and retrosternal (RS) route have been used for reconstruction after minimally invasive esophagectomy (MIE), the optimal route remains controversial. This study reviewed our experiences with McKeown MIEs for esophageal cancer and aimed to investigate which route was better for esophageal reconstruction. MATERIALS AND METHODS: From December 2011 to December 2013, 103 patients who underwent McKeown MIE and esophageal reconstruction by PM or RS routes were reviewed. The decision regarding which approach was appropriated mainly depended on the first surgeon's preference and experience. Baseline demographics, operative, and postoperative data of the patients were analyzed. RESULTS: Fifty-six and forty-seven patients receiving PM and RS route reconstruction were reviewed, respectively. Shorter operation time (P = 0.001), less blood loss (P = 0.029), and longer route length (P < 0.001) were observed in PM route compared with RS route. No difference was observed in the resection type, harvested lymph node, intensive care unit and hospital stay, postoperative complications, and in-hospital mortality between the two routes (all P > 0.05). CONCLUSIONS: Both RS route and PM route were safe and effective. PM route was associated with shorter operation time, less blood loss, but longer route length compared with RS route.

Identification of lung adenocarcinoma subtypes and a prognostic signature based on activity changes of the hallmark and immunologic gene sets.

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Roles of the crucial mitochondrial DNA in hypertrophic cardiomyopathy prognosis and diagnosis: A review.

Mitochondrial DNA is implicated in hypertrophic cardiomyopathy (HCM) development. We aimed to identify valuable mtDNAs that contribute to the development of HCM. Differentially expressed mitochondrial DNAs (DEMGs) between HCM and controls were screened. GO and KEGG functional enrichment analyses were performed, and the optimum genes were explored using the LASSO regression mode and SVM-RFE model. A diagnostic scoring model was constructed and verified using ROC curves. Mitochondria-based subtypes were identified. Immune performance among the subtypes including immune cells, immune checkpoint genes, and HLA family genes was analyzed. Finally, an mRNA-transcription factor (TF)-miRNA network was constructed using Cytoscape software. Twelve DEMGs in HCM were selected. Among them, 6 DEMGs, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B were demonstrated as DEMGs at the point of intersection of Lasso regression and SVM-RFE. The ROC of the model for the training and validation datasets was 0.999 and 0.958, respectively. Two clusters were divided, and 4 immune cell types were significantly different between the 2 clusters, including resting mast cells, macrophages M2, and plasma cells. Nine upregulated KEGG pathways were enriched in cluster 1 vs. cluster 2 including O-glycan biosynthesis, the ErbB signaling pathway, and the GnRH signaling pathway. Meanwhile, 49 down-regulated pathways were enriched such as the toll-like signaling pathway and natural killer cell-mediated cytotoxicity pathway. The 6 gene-based mRNA-TF-miRNA networks included other 133 TFs and 18 miRNAs. Six DEMGs in HCM, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B, can be indicative of HCM prognosis or disease progression.

Study on the Correlation Between CT Features and Vascular Tumor Thrombus Together With Nerve Invasion in Surgically Resected Lung Adenocarcinoma.

Background: We aimed to analyze the relationship between pulmonary adenocarcinoma patients with vascular tumor thrombus and nerve invasion and different CT features. Methods: The preoperative CT scanning data of 86 patients with lung adenocarcinoma who underwent surgical resection in our hospital from January 2020 to January 2022 were analyzed in the form of retrospective analysis. The CT images of all patients were observed, and the relationship between them and vascular tumor thrombus and nerve invasion of lung adenocarcinoma was analyzed. At the same time, the sensitivity, specificity, and accuracy of enhanced CT and plain CT were compared to evaluate the diagnostic efficacy of both. Results: The results showed that the vascular tumor thrombus of lung adenocarcinoma was mainly related to the solid components and lobulated and calcified tumors in CT images, and the nerve invasion of lung adenocarcinoma was mainly related to the tumors with bronchial inflation sign in CT images (P < 0.05). The sensitivity, specificity, and accuracy of enhanced CT in the diagnosis of vascular tumor thrombus were 78.26%, 96.83%, and 91.86%, respectively, and the sensitivity, specificity, and accuracy in the diagnosis of nerve invasion were 75.00%, 98.72%, and 96.51%, respectively. The sensitivity, specificity, and accuracy of plain CT in the diagnosis of vascular tumor thrombus were 43.48%, 92.06%, and 79.07%, respectively, and the sensitivity, specificity, and accuracy in the diagnosis of nerve invasion were 25.00%, 94.87%, and 88.37%, respectively. The contrast showed that the sensitivity and accuracy of enhanced CT were higher than those of plain CT (P < 0.05), but the difference of specificity was not obvious (P > 0.05). Conclusions: Solid components and lobulated and calcified tumors in CT signs are closely related to vascular tumor thrombus of lung adenocarcinoma, while patients with bronchial inflation sign are related to nerve invasion.

Identification of prognostic values of the transcription factor-CpG-gene triplets in lung adenocarcinoma: A narrative review.

OBJECTIVE: Abnormal DNA methylation can regulate carcinogenesis in lung adenocarcinoma (LUAD), while transcription factors (TFs) mediate methylation in a site-specific manner to affect downstream transcriptional regulation and tumor progression. Therefore, this study aimed to explore the TF-methylation-gene regulatory relationships that influence LUAD prognosis. METHODS: Differential analyses of methylation sites and genes were generated by integrating transcriptome and methylome profiles from public databases. Through target gene identification, motif enrichment in the promoter region, and TF prediction, TF-methylation and methylation-gene relation pairs were obtained. Then, the prognostic TF-methylation-gene network was constructed using univariate Cox regression analysis. Prognostic models were constructed based on the key regulatory axes. Finally, Kaplan-Meier curves were created to evaluate the model efficacy and the relationship between candidate genes and prognosis. RESULTS: A total of 1878 differential expressed genes and 1233 differential methylation sites were screened between LUAD and normal samples. Then 10 TFs were predicted to bind 144 enriched motifs. After integrating TF-methylation and methylation-gene relations, a prognostic TF-methylation-gene network containing 4 TFs, 111 methylation sites, and 177 genes was constructed. In this network, ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were selected to construct the prognostic models, which showed robust abilities in predicting 1-, 3-, and 5-year survival probabilities. Finally, ERG and MTURN were downregulated in LUAD samples, whereas FOXM1 and PTPR were upregulated. Their expression levels were related to LUAD prognosis. CONCLUSION: ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were proposed as potential biomarkers for predicting the prognosis of LUAD.

Analysis of microRNA expression profile identifies novel biomarkers for non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer mortality. MicroRNAs (miRNAs), small noncoding RNAs, regulate the expression of genes that play roles in human cancer via posttranscriptional inhibition. METHODS: To identify the potential miRNA biomarkers in NSCLC, we downloaded the miRNA expression profile (ID: GSE29248) of NSCLC from the Gene Expression Omnibus (GEO) database and analyzed the differentially expressed miRNAs in NSCLC tissue compared with normal control tissue. Then the targets of these differentially expressed miRNAs were screened and used in network construction and functional enrichment analysis. RESULTS: We identified a total of 17 miRNAs that showed a significantly differential expression in NSCLC tissue. We found that miR-34b and miR-520h might play important roles in the regulation of NSCLC, miR-22 might be a novel biomarker as an oncogene, and miR-448 might promote, while miR-654-3p prevents, NSCLC progression. CONCLUSIONS: Our study may provide the groundwork for further clinical molecular target therapy experiments in NSCLC.BAC