Risk factors, prognostic factors, and nomograms for distant metastases in patients with gastroenteropancreatic neuroendocrine tumors: a population-based study.

Background: Patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor prognosis for distant metastasis. Currently, there are no studies on predictive models for the risk of distant metastasis in GEP-NETs. Methods: In this study, risk factors associated with metastasis in patients with GEP-NETs in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by univariate and multivariate logistic regression, and a nomogram model for metastasis risk prediction was constructed. Prognostic factors associated with distant metastasis in patients with GEP-NETs were analyzed by univariate and multivariate Cox, and a nomogram model for prognostic prediction was constructed. Finally, the performance of the nomogram model predictions is validated by internal validation set and external validation set. Results: A total of 9145 patients with GEP-NETs were enrolled in this study. Univariate and multivariate logistic analysis demonstrated that T stage, N stage, tumor size, primary site, and histologic types independent risk factors associated with distant metastasis in GEP-NETs patients (p value < 0.05). Univariate and multivariate Cox analyses demonstrated that age, histologic type, tumor size, N stage, and primary site surgery were independent factors associated with the prognosis of patients with GEP-NETs (p value < 0.05). The nomogram model constructed based on metastasis risk factors and prognostic factors can predict the occurrence of metastasis and patient prognosis of GEP-NETs very effectively in the internal training and validation sets as well as in the external validation set. Conclusion: In conclusion, we constructed a new distant metastasis risk nomogram model and a new prognostic nomogram model for GEP-NETs patients, which provides a decision-making reference for individualized treatment of clinical patients.

Influences of Fast Track Surgery Concept-based High-quality Medical Service on Postoperative Symptom Improvement and Safety among Patients with Lung Cancer.

Objective: To investigate the impacts of the fast track surgery (FTS) concept on postoperative symptom improvement and complication incidence among lung cancer patients. Methods: 100 patients diagnosed with lung cancer after the detection of pulmonary nodules in the hospital (January 2020 to December 2021) were included as research subjects. 50 patients in the control group received routine nursing, while 50 patients in the experimental group underwent FTS nursing based on routine nursing. Preoperative and postoperative stress reactions, operation-related information, degree of pain, nursing satisfaction, and complications among included patients were summarized. Results: According to the results, the heart rate in the experimental group 72 hours after the operation was superior to that in the control group (P < .05). Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in the experimental group were lower than those in the control group. The differences demonstrated statistical significance (P < .05). Mean arterial pressure (MAP) in the experimental group 12 hours after the operation was lower than that in the control group (P < .05). The length of hospital stays and chest drainage tube indwelling duration in the experimental group were shorter than those in the control group (P < .05). The degree of pain experienced by patients in the experimental group apparently reduced 3 days after operation (P < .05). The total incidence of complications in the experimental group was lower than that recorded for patients in the control group (P < .05). Nursing satisfaction in the experimental group was superior to that in the control group and the difference revealed statistical significance (P < .05). Conclusions: The study verified the safety and efficacy of FTS concept-based operation on patients with lung cancer.

Relationship between early lung adenocarcinoma and multiple driving genes based on artificial intelligence medical images of pulmonary nodules.

Lung adenocarcinoma is one of the most common cancers in the world, and accurate diagnosis of lung nodules is an important factor in reducing its mortality. In the diagnosis of pulmonary nodules, artificial intelligence (AI) assisted diagnosis technology has been rapidly developed, so testing its effectiveness is conducive to promoting its important role in clinical practice. This paper introduces the background of early lung adenocarcinoma and lung nodule AI medical imaging, and then makes academic research on early lung adenocarcinoma and AI medical imaging, and finally summarizes the biological information. In the experimental part, the relationship analysis of 4 driver genes in group X and group Y showed that there were more abnormal invasive lung adenocarcinoma genes, and the maximum uptake value and uptake function of metabolic value were also higher. However, there was no significant correlation between mutations in the four driver genes and metabolic values, and the average accuracy of AI-based medical images was 3.88% higher than that of traditional images.

Circ_0060967 facilitates proliferation, migration, and invasion of non-small-cell lung cancer cells by sponging miR-660-3p/UBN2.

Growing evidence has implied that circular RNAs (circRNAs) are involved in multiple tumors progression. This study firstly uncovered the function of circ_0060967 in non-small-cell lung cancer (NSCLC) progression. Quantitative real-time polymerase chain reaction was employed to monitor circ_0060967, miR-660-3p, and ubinuclein-2 (UBN2) mRNA expression in clinical tissues and cell lines. Cell counting kit-8 assay, 5-ethynyl-20-deoxyuridine assay, and Transwell assay were recruited to research cells viability, proliferation, migration, and invasion. BALB/c nude mice were applied to perform in vivo study. Fluorescence in situ hybridization was adopted to explore the subcellular location of circ_0060967 in NSCLC cells. Dual luciferase reporter gene assay and RNA pull-down assay were utilized to identify the interaction among circ_0060967, miR-660-3p, and UBN2. Western blot was employed for UBN2 protein expression investigation in NSCLC cells. Immunohistochemistry was utilized to research UBN2 protein expression in clinical tissues and xenograft tumor tissues. Circ_0060967 was aberrantly over-modulated in NSCLC tissues and cells. High circ_0060967 expression implied grim prognosis. Loss of circ_0060967 weakened NSCLC cells viability, proliferation, migration, invasion, and in vivo growth. Circ_0060967 was mainly distributed in the cytoplasm of NSCLC cells. Down-modulated miR-660-3p and up-regulated UBN2 were found in NSCLC patients. miR-660-3p was sponged by circ_0060967 and it directly targeted UBN2. miR-660-3p down-modulation rescued the suppression of circ_0060967 loss on NSCLC cells viability, proliferation, migration, and invasion. Circ_0060967 facilitated NSCLC progression by enhancing UBN2 expression via sponging miR-660-3p. It might be a promising target for NSCLC treatment.

Effect of PFKFB4 on the Prognosis and Immune Regulation of NSCLC and Its Mechanism.

Background: NSCLC (non-small cell lung cancer) has become the malignancy with the highest incidence and mortality rate worldwide. Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a key regulator of glycolysis with both kinase and phosphatase activities. The Warburg effect, or increased glycolysis in tumors, provides the metabolic basis for cancer cell proliferation and metastasis, and the Warburg pathway enzyme PFKFB4 is a newly identified important kinase. This study aimed to elucidate the poor prognostic relevance of PFKFB4 in non-small cell lung cancer tissues and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Methods: In this study, immunohistochemical methods were used to assess PFKFB4 expression levels in 140 surgical specimens from patients with histologically confirmed non-small cell lung cancer and to investigate the relationship between PFKFB4 expression levels and the patients' clinicopathological characteristics. The impact of PFKFB4 expression on prognosis was evaluated using Kaplan-Meier survival analysis and Cox regression analysis. Results: When compared to normal paracrine tissues, PFKFB4 expression was enhanced in lung cancer tissues, and Kaplan-Meier survival analysis revealed that patients with high PFKFB4 expression had a worse prognosis. In NSCLC, PFKFB4 was found to be associated with immune cell infiltration and immunological checkpoints. Conclusion: PFKFB4 expression may be upregulated as a sign of poor prognosis in NSCLC, and PFKFB4 may be implicated not only in the genesis and progression of NSCLC but also in its immunological control.

Corrigendum: Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer.

[This corrects the article DOI: 10.3389/fonc.2022.781903.].

The Effect of the Appropriate Timing of Radiotherapy on Survival Benefit in Patients with Metastatic Esophageal Cancer Who Have Undergone Resection of Primary Site: A SEER Database Analysis.

Background: Metastatic esophageal cancer (MEC) is an advanced stage of esophageal cancer. However, still, resection of primary site and radiotherapy are considered treatment modalities to treat patients with MEC. Hence, this study is aimed at exploring the effect of the appropriate timing of radiotherapy on the survival benefit of these patients by comparing cancer-specific survival (CSS). Method: The patient information was obtained from the National Surveillance Epidemiology and End Results (SEER) database between the years 2004 and 2017. We used the SEER∗ STAT (V8.3.9.2) software to search and download data. Patients treated with pre- and postoperative radiotherapy were divided into two groups. The propensity score matching (PSM) analysis was performed to increase the comparability of data within two groups. We used the Kaplan-Meier method to analyze and compare the CSS between the two groups. The Cox risk model was used to analyze variables affecting patient survival. Results: A total of 599 patients with MEC who experienced resection of the primary site and radiotherapy were recruited. 144 pairings formed through PSM. The 5-year CSS was 23.0% and 11.7% for patients who have undergone pre- and postoperative radiotherapy, respectively. Patients who have undergone preoperative radiotherapy showed better CSS than those who received postoperative radiotherapy (P < 0.001). The multivariate Cox analysis of the entire cohort showed that age > 60 years at the time of diagnosis (HR = 1.481, 95% CI: 1.1341-1.934, and P = 0.04) and other histological types of esophageal cancer (HR = 1.581, 95% CI: 1.067-2.341, and P = 0.022) increased the risk of cancer-related death. Inversely, marriage (HR = 0.696, 95% CI: 0.514-0.942, and P = 0.019) and preoperative radiotherapy (HR = 0.664, 95% CI: 0.517-0.853, and P < 0.001) reduced the risk of death from cancer. Conclusions: For patients with MEC, preoperative radiotherapy might have a significant effect on the survival benefit over those who receive postoperative radiotherapy.

Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer.

BACKGROUND: Studies have demonstrated that the regulatory role of competitive endogenous RNA (ceRNA) networks is closely related to tumorigenesis, which provides new targets for tumor therapy. In this study, the focus was to explore the ceRNA networks that regulate SLC6A8 expression and their prognosis in non-small cell lung cancer (NSCLC). METHODS: Firstly, the Cancer Genome Atlas (TCGA) data combined with immunohistochemical staining was used to compare SLC6A8 expression in NSCLC tissues and normal tissues. Thereafter, samples from the immunohistochemical staining of NSCLC were integrated with clinical follow-up data for prognostic analysis. The Starbase database was employed to search for SLC6A8-targeted miRNAs and lncRNAs, and survival analysis was performed using clinical data from TCGA to obtain SLC6A8 expression and prognosis-related ceRNA networks. Finally, the prognostic and therapeutic prospects of SLC6A8 in NSCLC were further analyzed from methylation sites and the immune microenvironment. RESULTS: The study results revealed that SLC6A8 was significantly overexpressed in NSCLC tissues compared to normal tissues, and clinical follow-up data showed that the overexpression group was associated with poor prognosis. In addition, the Starbase data combined with TCGA clinical data analysis demonstrated that the AL513318.2/hsa-miR-26a-5p/SLC6A8 network regulates SLC6A8 overexpression in NSCLC and is associated with poor prognosis. Methylation analysis revealed that 11 methylation sites were closely associated with the prognosis of NSCLC. In addition, the immune prognostic risk model showed that the high-risk group was associated with a poorer prognosis than the low-risk group, despite showing a better immunotherapy outcome. CONCLUSION: In summary, the AL513318.2/hsa-miR-26a-5p/SLC6A8 network upregulates SLC6A8 expression in NSCLC and is associated with poor prognosis. Therefore it may be a prognostic biomarker of NSCLC and a potential therapeutic target.

Correlation of SIDT1 with Poor Prognosis and Immune Infiltration in Patients with Non-Small Cell Lung Cancer.

PURPOSE: To investigate the expression profile of systemic RNA interference deficient-1 transmembrane family member 1 (SIDT1) in patients with non-small cell lung cancer (NSCLC) and assess its prognostic value and immune infiltration. MATERIALS AND METHODS: A tissue microarray (TMA) was purchased containing 60 paired NSCLC tissues and matched para-tumor tissues, and another TMA was constructed comprising 140 NSCLC tissues. Then, immunohistochemical staining and scoring were performed. Finally, we evaluated the expression profiles and prognostic values of SIDT1 in NSCLC. Correlation between SIDT1 gene expression and the immune microenvironment of NSCLC was investigated using the ESTIMATE and CIBERSORT algorithms. RESULTS: SIDT1 was mainly detected in the cytoplasm and the cell membrane. SIDT1 expression was significantly higher in tumor tissues than in para-tumor tissues. High expression of SIDT1 was correlated with the NSCLC stage. High SIDT1 expression signals worsening overall survival (OS) in NSCLC patients, especially in stage I. In LUSC, high SIDT1 expression is an independent prognostic factor for worsening OS. CONCLUSION: High SIDT1 expression predicted a low survival rate in LUSC patients, suggesting it may be a potential target for prognostic assessment of NSCLC patients.

NCAPG is a prognostic biomarker of immune infiltration in non-small-cell lung cancer.

Purpose: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. The protein NCAPG plays a significant role in tumor development. Patients & methods: We set up a tissue microarray (containing 140 NSCLC and ten normal lung tissues) and performed immunohistochemistry to assess NCAPG expression in the tissues of 140 patients. The prognostic value of NCAPG in NSCLC was assessed using the univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. We analyzed the association between NCAPG and immune infiltration in NSCLC. Results: Multifactorial analysis and Kaplan-Meier plots revealed that upregulation of NCAPG expression was an independent factor in the prognosis of NSCLC. Data from CIBERSORT showed a negative correlation between NCAPG and the expression of memory CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, mast cells and natural killer cells (p < 0.001). Gene set enrichment analysis revealed that cell cycle, adhesion and proliferation were significantly enriched in samples with a high NCAPG expression. Conclusion:NCAPG is a novel biomarker of prognosis and is associated with immune cell infiltration in the tumor microenvironment. Thus it may be a potential target in NSCLC treatment.

Circular RNA-UBE2D2 accelerates the proliferation and metastasis of non-small cell lung cancer cells via modulating microRNA-376a-3p/Eukaryotic Translation Initiation Factor 4γ2 axis.

Non-small cell lung cancer (NSCLC) ranks first in the morbidity and mortality of malignant tumors in China. As reported, circular RNAs (circRNAs) are emerged in the progress of NSCLC. The study was to figure out the potential mechanism of circ-UBE2D2 in the progression of NSCLC. First, plasmid vectors intervening circ-UBE2D2, microRNA (miR)-376a-3p or Eukaryotic Translation Initiation Factor 4γ2 (EIF4G2) expression were transfected into NSCLC cells, and the expression of circ-UBE2D2, miR-376a-3p and EIF4G2 was detected by reverse transcription quantitative polymerase chain reaction or Western blot. Then, cell proliferation was detected by Cell counting kit-8 assay and plate cloning. Cell apoptosis was tested by flow cytometry. Plate scratches and Transwell were used to detect cell migration and invasion. Finally, the binding sites of circRNA UBE2D2, EIF4G2 and miR-376a-3p were verified by bioinformatics website starBase analysis and dual luciferase reporter gene assay. The results manifested the up-regulation of circ-UBE2D2 expression in NSCLC tissues and cells. Circ-UBE2D2 promoted the proliferation, migration and invasion, but repressed apoptosis of NSCLC cells. Interestingly, circ-UBE2D2 directly targeted miR-376a-3p and up-regulated miR-376a-3p restrained proliferation, migration and invasion, but accelerated apoptosis of NSCLC cells. More importantly, EIF4G2 was the target of miR-376a-3p, and overexpression of EIF4G2 reversed the effects of circ-UBE2D2 downregulation on proliferation, migration, invasion and apoptosis of NSCLC cells. These results suggest that circ-UBE2D2 promotes the proliferation, migration and invasion but restrains apoptosis of lung cancer cells by regulating miR-376a-3p/EIF4G2 axis.

Hsa_circ_0016760 exacerbates the malignant development of non­small cell lung cancer by sponging miR­145­5p/FGF5.

Hsa_circ_0016760 expression has been reported to be increased in non­small cell lung cancer (NSCLC). The present study was designed to explore the role and mechanism of hsa_circ_0016760 in regulating NSCLC progression. In total, 60NSCLC patients were followed­up for 60 months after surgery. Hsa_circ_0016760 expression in tumor tissues and adjacent non­tumor tissues of NSCLC patients was explored by reverse transcription quantitative polymerase chain reaction (RT­qPCR). NSCLC cell proliferation was monitored by CCK­8 assay and EdU experiment. Transwell assays were used for the detection of NSCLC cell migration and invasion. The target of hsa_circ_0016760 (or miR­145­5p) was validated by luciferase reporter gene assay and RNA immunoprecipitation experiment. A xenograft model was studied with nude mice. Immunohistochemical staining was applied for the detection of Ki67 expression in xenograft tumors. Hsa_circ_0016760/miR­145­5p/FGF5 expression in tissues and cells was investigated by RT­qPCR and western blotting. Hsa_circ_0016760 was aberrantly upregulated in NSCLC, which was associated with poor prognosis of patients (P<0.05). Hsa_circ_0016760 silencing suppressed NSCLC cell proliferation, migration and invasion in vitro (P<0.01). Hsa_circ_0016760 facilitated FGF5 expression via sponging miR­145­5p. The miR­145­5p upregulation or FGF5 downregulation reversed the promoting effect of hsa_circ_0016760 on NSCLC cell proliferation, migration and invasion in vitro (P<0.01). In addition, hsa_circ_0016760 silencing inhibited tumor growth in vivo (P<0.01), and decreased Ki67 expression in xenograft tumors. In conclusion, hsa_circ_0016760 exacerbated the malignant development of NSCLC by sponging miR­145­5p/FGF5.

microRNA-195 Promotes Small Cell Lung Cancer Cell Apoptosis via Inhibiting Rap2C Protein-Dependent MAPK Signal Transduction.

This study aimed to explore the influences of microRNA-195 (miRNA-195)/Rap2C/MAPK in the proliferation and apoptosis of small cell lung cancer (SCLC) cells. QRT-PCR analysis were executed to evaluate miRNA-195 expression in lung cancer tissues and SCLC cells, and the western blot was implemented to monitor Rap2C protein level and uncovered whether the MAPK signaling pathway in lung cancer tissues and SCLC cells was activated. The CCK-8 experiment was performed to detect cell proliferation ability, and the flow cytometry was utilized to examine cell apoptosis level. Luciferase reporter gene system was executed to disclose the interaction between miRNA-195 and Rap2C. Subcutaneous implantation mouse models of SCLC cells were constructed to detect cell proliferation in vivo, and Kaplan-Meier method calculated patient survival. The expression of Rap2C was higher in lung cancer tissues and SCLC cells than in normal tissues and cells, while the expression of miRNA-195 was lower in lung cancer tissues and SCLC cells than in normal tissues and cells. miRNA-195 lower expression predicted showed reduced overall survival in lung cancer patients. Further loss of function and enhancement experiments revealed that miRNA-195 overexpression could significantly inhibit SCLC cell proliferation and promote cell apoptosis by upregulation of Bax and down-regulation of bcl-2; Luciferase reporter assay demonstrated that miRNA-195 could bind to Rap2C mRNA and inhibit its expression, Rap2C overexpression also related to the poorer prognosis of lung patients. Knockdown of Rap2C suppressed cell proliferation and expedited apoptosis. In addition, overexpression of Rap2C reversed miRNA-195-induced apoptosis and proliferation inhibition. Furthermore, miRNA195 prohibited the activation of MAPK signaling pathway by down-regulating Rap2C. These consequences indicated that miRNA-195 promotes the apoptosis and inhibits the proliferation of small cell lung cancer (SCLC) cells via inhibiting Rap2C protein-dependent MAPK signal transduction.

Effect of Aldosterone on Senescence and Proliferation Inhibition of Endothelial Progenitor Cells Induced by Sirtuin 1 (SIRT1) in Pulmonary Arterial Hypertension.

BACKGROUND Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary circulatory resistance. Pulmonary vascular endothelial dysfunction is one of the main causes of primary PAH. Endothelial progenitor cells (EPCs) can proliferate and differentiate into vascular endothelial cells and play an important role in maintaining normal endothelial function. Mineralocorticoid receptor inhibitor has been reported to be used in the treatment of PAH. However, the role and the underlying mechanism of aldosterone (ALDO) in PAH remains unclear. MATERIAL AND METHODS Rats were divided to 4 groups (n=10 per group) and treated with 0.9% normal saline, monocrotaline (MCT), spironolactone (SP), or MCT combined with SP. After the rats were sacrificed with an overdose of pentobarbital sodium, hematoxylin and eosin staining was performed to observe the pulmonary artery pathology section. Sirtuin 1 (SIRT1), p53, and p21 protein expression was detect by western blot. Immunofluorescence staining was performed to verify EPCs. EPCs were treated with different concentrations of ALDO. MTT assay and senescence-associated ß-galactosidase staining were used to measure cell viability and senescence. RESULTS MCT increased the vascular arterial wall thickness and wall area, inhibited SIRT1 protein expression and increased p53 and p21 protein expression in the lung tissue of rats, while SP partially reversed this effect. In addition, ALDO inhibited EPCs viability and induced senescence. The expression of p53 and p21 proteins in the EPCs were upregulated and the senescence was accelerated when EPCs were transfected with SIRT1 siRNA. CONCLUSIONS ALDO promoted EPCs senescence and inhibited EPCs proliferation by downregulating SIRT1, which regulates the p53/p21 pathway, thus promoting PAH.

Evaluation of the Role of hsa-mir-124 in Predicting Clinical Outcome in Breast Invasive Carcinoma Based on Bioinformatics Analysis.

PURPOSE: Breast invasive carcinoma (BRCA) is the most common malignant tumor. MiR-124 plays a tumor-suppressive role in human cancer. However, the clinical significance of miR-124 in BRCA remains unclear. The aim of this study was to evaluate the association of hsa-mir-124 expression and the clinicopathological characteristics in BRCA using database analysis. METHODS: The clinical data and expression profiles of hsa-mir-124 were obtained from the cancer genome atlas for BRCA (TCGA_BRCA). Then, the prognostic value of hsa-mir-124 in BRCA was investigated using the Cox Regression test, and the association of hsa-mir-124 and pathology TNM stages and pathologic stages were measured by the Kruskal-Wallis test and Wilcox. test. In addition, the association of hsa-mir-124 and tumor molecular phenotypes was performed using the Chi-Square test. RESULTS: We found that the overall survival of patients with high expression of hsa-mir-124-1 and hsa-mir-124-2 was better than that of patients with low expression of hsa-mir-124-1 and hsa-mir-124-2. And the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was mainly enriched in T1/T2 stages, NO/N1 stages, and M0 stages. Then, the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was negatively associated with tumor lymph node metastasis. Moreover, the expression of hsa-mir-124 was associated with tumor molecular phenotype in breast invasive carcinoma. CONCLUSION: Our findings indicated that hsa-mir-124 expressions were associated with overall survival, TNM stages, pathologic characteristics, and tumor molecular phenotype in BRCA via TCGA_BRCA database, providing a new biomarker and a potential therapeutic target for BRCA patients.

TRIM59 as a novel molecular biomarker to predict the prognosis of patients with NSCLC.

As a member of the tripartite motif family, tripartite motif-containing protein 59 (TRIM59) serves as an E3 ubiquitin ligase in various cellular processes, including intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy and carcinogenesis. The present study aimed to investigate the expression and prognostic value of TRIM59 in patients with non-small cell lung cancer (NSCLC). Expression of TRIM59 in patients with NSCLC was measured by immunohistochemistry in tissue microarrays. Datasets from The Cancer Genome Atlas (TCGA) were used to further verify the expression level of TRIM59 in NSCLC, lung adenocarcinoma and lung squamous cell carcinoma (LUSC). The prognostic value of TRIM59 in NSCLC was also analyzed. Immunohistochemistry revealed that TRIM59 was primarily located in the cytoplasm of tumor cells. Analysis of TCGA datasets revealed that TRIM59 was more highly expressed in tumor tissues than in normal tissues (P<0.0001). Furthermore, the TRIM59 expression level was associated with tumor differentiation (P=0.012), while no association was observed between TRIM59 expression and any other clinicopathological parameters. However, the average overall survival rate of patients with NSCLC in the high TRIM59 expression group was significantly lower than that in the low expression group (P=0.014), especially in patients with LUSC (P=0.016) and patients with poor differentiation (P=0.033). The multivariate analysis indicated that high TRIM59 expression is an independent prognostic factor in patients with NSCLC (P=0.018) and was associated with poor prognosis in patients with NSCLC. Therefore, TRIM59 may serve as a novel molecular biomarker to predict the prognosis of patients with NSCLC.

High throughput sequencing identifies breast cancer-secreted exosomal LncRNAs initiating pulmonary pre-metastatic niche formation.

OBJECTIVE: Increasing evidence indicated that cancer-secreted exosomes played an important role in tumor metastasis. However, the function of exosomes in breast cancer pulmonary metastasis remains unknown. The aim of the study was to investigate the role of exosome-derived from breast cancer-secreted long non-coding RNAs (LncRNAs) on pre-metastatic niche formation in pulmonary metastasis. METHODS: Exosomes-derived from breast cancer were separated by ultracentrifugation. The high-throughput sequencing, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to detect and evaluate the differential expression of LncRNAs in lung fibroblasts with exosomes treated. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify candidate LncRNAs expression. RESULTS: We found that exosomes-derived from breast cancer induced lung fibroblasts proliferation and migration. In addition, a large number of LncRNAs expression abnormalities were involved in the breast cancer lung metastasis microenvironment. CONCLUSION: Our findings suggested that exosomal LncRNAs facilitated tumor pre-metastatic niche formation and represented a novel mechanistic insight into the molecular mechanism of cancer metastasis microenvironment.

ARHGAP30 suppressed lung cancer cell proliferation, migration, and invasion through inhibition of the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Rho GTPase-activating protein 30 (ARHGAP30), a member of the Rho GTPase-activating proteins (Rho GAPs) family, plays an important role in the regulation of cytoskeleton organization and cell adhesion. MATERIALS AND METHODS: mRNA and protein expression was assessed by quantitative real-time PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and Transwell assays were conducted to detect cell proliferation, migration, and invasion. RESULTS: ARHGAP30 expression was downregulated in specimens and cell lines of lung cancer in comparison to non-cancerous specimens and normal bronchial epithelial cell lines, respectively. Moreover, in vitro experiments demonstrated that ARHGAP30 overexpression impeded the proliferative, migratory, and invasive abilities of lung cancer cells. Moreover, bioinformatics analysis with The Cancer Genome Atlas (TCGA) lung cancer dataset showed a negative association between ARHGAP30 expression and the Wnt signaling pathway. Enforced expression of ARHGAP30 decreased the mRNA and protein levels of ß-catenin, c-Myc, matrix metalloproteinase-2 (MMP-2) and MMP-9. Besides, the ß-catenin inhibitor XAV939 blocked the enhanced cell growth, migration, and invasion caused by ARHGAP30 knockdown. Thus, the Wnt/ß-catenin pathway mediated the functions of ARHGAP30 in lung cancer cells. CONCLUSION: ARHGAP30 acts as a tumor suppressor in lung cancer by suppressing Wnt/ß-catenin signaling.

Survival analysis in Caucasian pulmonary adenocarcinoma patients based on differential targets between Caucasian and Asian population.

Ethnicity differences may contribute to the variety of overall survival in pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic driver mutations (ERSDM) profile on Caucasian survival is not well investigated. In this study, we studied epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes were selected as harboring somatic driver mutations with >10% prevalence and with different occurrence between Caucasian and Asian ethnicity. Clinical information and transcriptome sequencing of 173 Caucasian pulmonary adenocarcinoma patients with matched mutation data are retrieved from TCGA, Kaplan-Meier analyses and Cox proportional-hazards regression models are further used to analyze the effect of the ERSDM profile on overall survival. There is no significant correlation between single gene mutation and overall survival, while patients with less than two mutated genes have a better overall survival compared with those with at least two mutated genes (p = 0.034). All of these indicate that multiple mutations in the ERSDM profile may be a negative prognostic factor for overall survival in Caucasian pulmonary adenocarcinoma patients.

Triptolide exhibits antitumor effects by reversing hypermethylation of WIF­1 in lung cancer cells.

Triptolide (TP) exhibits numerous biological activities, including immunosuppressive, anti­inflammatory and antitumor effects. The aim of the present study was to investigate the role of TP as a potent therapeutic drug for the treatment of lung cancer and to investigate the underlying therapeutic mechanisms. Western blot analyses and reverse transcription­quantitative polymerase chain reaction (PCR) were performed to investigate the expression of genes at transcriptional and translational levels, respectively. Methylation­specific PCR assays were conducted to investigate whether TP affects the Wnt inhibitory factor­1 (WIF­1) methylation status and subsequently affects apoptosis, migration or the invasion of lung cancer cells. The results of the present study revealed that the methylation status of WIF­1 in lung cancer cell lines A549 and H460 was significantly enhanced compared with the human normal bronchial epithelial cell line HBE, whereas treatment with TP was revealed to induce the demethylation of WIF­1. The present study aimed to investigate whether the biological activities of TP are regulated by inhibiting the Wnt signaling pathway via an increase in WIF­1 expression levels. The results of the present study revealed that Wnt signaling was suppressed in cells following treatment with TP, which was concluded by the downregulation of Axin 2 and ß­catenin expression. Further investigation demonstrated that the silencing of WIF­1 expression with small interfering RNA reversed the TP­induced upregulation of WIF­1 expression, upregulated Axin 2 and ß­catenin expression and enhanced the activation of Wnt signaling. Notably, an upregulation of cellular tumor antigen p53 expression, and downregulation of matrix metalloproteinase­9 (MMP­9) and phosphorylated­nuclear factor­κB (NF­κB) P65 (p­P65) levels was observed following TP treatment. These results suggest that the Wnt, p53 and NF­κB signaling pathways mediate the potent antitumor effects of TP. Notably, the silencing of WIF­1 did not completely recover the levels of p53, MMP­9 and p­P65 in cells treated with TP compared with the control cells, thus suggesting that TP exhibits further functions in addition to the targeting of WIF­1.