Silencing of A-kinase anchor protein 4 inhibits the metastasis and growth of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The treatment of advanced NSCLC can be challenging due to drug resistance. The discovery of novel cancer-testis antigens to develop new strategies for advanced metastatic NSCLC is required. AKAP4 is an oncogene discovered in some malignant tumors, and its molecular function of AKAP4 in NSCLC is unknown. This study aimed to explore the potential function of AKAP4 in the development and progression of NSCLC. AKAP-4 was found to be significantly upregulated in both clinical NSCLC tissues and NSCLC cell lines. Cell viability and migration were suppressed, apoptosis was induced, and tube formation was inhibited by the knockdown of AKAP-4, accompanied by the downregulation of VEGF, N-cadherin, EphA2, and MMP-2, and upregulation of c-AMP, PKA, and E-cadherin. In vivo xenograft experiments revealed that tumor growth was inhibited by the knockdown of AKAP4, accompanied by the activation of c-AMP/PKA signaling and inhibition of epithelial-mesenchymal transition progression. Our results show that AKAP4 might be an important target for treating NSCLC because of its function in promoting the migration and proliferation of NSCLC cells.

Efficacy of Intraoperative Recurrent Laryngeal Nerve Monitoring During Thoracoscopic Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-Analysis.

Background: Recurrent laryngeal nerve paralysis (RLNP), a severe complication of mini-invasive esophagectomy, usually occurs during lymphadenectomy adjacent to recurrent laryngeal nerve. This systematic review and meta-analysis aimed to evaluate the efficacy of intraoperative nerve monitoring (IONM) in reducing RLNP incidence during mini-invasive esophagectomy. Methods: Systematic literature search of PubMed, EMBASE, EBSCO, Web of Knowledge, and Cochrane Library until June 4, 2021 was performed using the terms "(nerve monitoring) OR neuromonitoring OR neural monitoring OR recurrent laryngeal nerve AND (esophagectomy OR esophageal)." Primary outcome was postoperative RLNP incidence. Secondary outcomes were sensitivity, specificity, and positive and negative predictive values for IONM; complications after esophagectomy; number of dissected lymph nodes; operation time; and length of hospital stay. Results: Among 2,330 studies, five studies comprising 509 patients were eligible for final analysis. The RLNP incidence was significantly lower (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.12-0.88, p < 0.05), the number of dissected mediastinal lymph nodes was significantly higher (mean difference 4.30, 95%CI 2.75-5.85, p < 0.001), and the rate of hoarseness was significantly lower (OR 0.14, 95%CI 0.03-0.63, p = 0.01) in the IONM group than in the non-IONM group. The rates of aspiration (OR 0.31, 95%CI 0.06-1.64, p = 0.17), pneumonia (OR 1.08, 95%CI 0.70-1.67, p = 0.71), and operation time (mean difference 7.68, 95%CI -23.60-38.95, p = 0.63) were not significantly different between the two groups. The mean sensitivity, specificity, and positive and negative predictive values for IONM were 53.2% (0-66.7%), 93.7% (54.8-100%), 71.4% (0-100%), and 87.1% (68.0-96.6%), respectively. Conclusion: IONM was a feasible and effective approach to minimize RLNP, improve lymphadenectomy, and reduce hoarseness after thoracoscopic esophagectomy for esophageal cancer, although IONM did not provide significant benefit in reducing aspiration, pneumonia, operation time, and length of hospital stay.

The Impact of Skip vs. Non-Skip N2 Lymph Node Metastasis on the Prognosis of Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Objective: The skip N2 metastases were frequent in non-small-cell lung cancer (NSCLC) and the better prognosis of NSCLC with a skip over non-skip N2 lymph node metastases is controversial. The primary aim of this study is to investigate the prognosis effect of skip N2 lymph node metastases on the survival of NSCLC. Setting: A literature search was conducted in PubMed, EMBASE, and Cochrane Library with the term of "N2" or "mediastinal lymph node" or "mediastinal nodal metastases", and "lung cancer" and "skip" or "skipping" in the title/abstract field. The primary outcomes of interests are 3- and 5-year survival in NSCLC. Participants: Patients who underwent complete resection by lobectomy, bilobectomy, or pneumonectomy with systemic ipsilateral lymphadenectomy and were staged as pathologically N2 were included. Primary and Secondary Outcome Measures: The 3- and 5-year survival of NSCLC was analyzed. The impact of publication year, number of patients, baseline mean age, gender, histology, adjuvant therapy, number of skip N2 stations, and survival analysis methods on the primary outcome were also analyzed. Results: A total of 21 of 409 studies with 6,806 patients met the inclusion criteria and were finally included for the analysis. The skip N2 lymph node metastases NSCLC had a significantly better overall survival (OS) than the non-skip N2 NSCLC [hazard ratio (HR), 0.71; 95% CI, 0.62-0.82; P < 0.001; I 2 = 40.4%]. The skip N2 lymph node metastases NSCLC had significantly higher 3- and 5-year survival rates than the non-skip N2 lymph node metastases NSCLC (OR, 0.75; 95% CI, 0.66-0.84; P < 0.001; I 2 = 60%; and OR, 0.78; 95% CI, 0.71-0.86; P < 0.001; I 2 = 67.1%, respectively). Conclusion: This meta-analysis suggests that the prognosis of skip N2 lymph node metastases NSCLC is better than that of a non-skip N2 lymph node.

Pulmonary function after segmentectomy versus lobectomy in patients with early-stage non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: Segmentectomy is widely performed for early-stage lung cancer. However, the effects of segmentectomy versus lobectomy on pulmonary function remain unclear. We performed a meta-analysis with the aim of comparing segmentectomy and lobectomy in terms of preservation of pulmonary function in patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: We conducted a literature search of PubMed using the terms 'pulmonary function' AND 'segmentectomy' AND 'lobectomy'. The primary outcomes of interest were the forced expiratory volume in 1 second (FEV1), FEV1 as percent of predicted (%FEV1), change in FEV1 (Δ%FEV1), and the ratio of postoperative to preoperative FEV1. RESULTS: Thirteen studies comprising 2027 patients met the inclusion and exclusion criteria and were included for analysis, including 787 patients in the segmentectomy group and 1240 patients in the lobectomy group. Patients in the segmentectomy group showed significantly better preservation of FEV1 and %FEV1 compared with the lobectomy group. The reduction in FEV1 after surgery was significantly less in the segmentectomy group compared with the lobectomy group, and Δ%FEV1 was significantly higher in the segmentectomy group than in the lobectomy group. CONCLUSION: Segmentectomy results in better preservation of pulmonary function compared with lobectomy in patients with early-stage NSCLC.

Identification of a ferroptosis-related gene signature (FRGS) for predicting clinical outcome in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Ferroptosis, an oxidative, iron-dependent form of necrotic cell death, is highly associated with tumorigenesis and cancer progression. However, the prognostic value of ferroptosis progress in LUAD was still rarely be investigated. METHODS: Herein, we collected three mRNA expression profiles and 85 ferroptosis-related genes from public databases. The "limma" package was used to identify ferroptosis-related differentially expressed genes (DEGs). Univariate Cox regression analysis and LASSO regression analysis were applied to screen and develop a ferroptosis-related gene signature (FRGS) and a formula to calculate the risk score. Multivariate Cox regression analysis was implemented to determine independent prognostic predictors of overall survival (OS). The area under the receiver operating characteristic curve (AUC) and calibration plot were used to evaluate the predictive accuracy of the FRGS and nomogram. RESULTS: We developed a FRGS with five genes (CYBB, CISD1, FADD, SAT2, VDAC2). The AUC of the FRGS in TCGA cohort was 0.777 at 1-year, 0.721 at 3-year and 0.725 at 5-year, significantly superior to the AUC of TNM stage (1-year: 0.701, 3-year: 0.691, 5-year: 0.686). A similar phenomenon was observed in GEO cohort 1 and 2. Multivariate Cox regression analysis indicted TNM stage and risk score were independent prognostic predictors. Finally, we built a nomogram with TNM stage and FRGS, the AUCs of which markedly higher than that of FRGS or TNM stage alone. CONCLUSION: We constructed a prognostic FRGS with five ferroptosis-related genes and a nomogram for predicting the 1-, 3- and 5-year survival rate of LUAD patients, which may provide a new understanding of the prognostic value of ferroptosis progress in LUAD and will benefit prognosis assessment of LUAD patients.

Identification of P2RY13 as an immune-related prognostic biomarker in lung adenocarcinoma: A public database-based retrospective study.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading histological subtype of non-small cell lung cancer (NSCLC). METHODS: In the present study, the gene matrixes of LUAD were downloaded from The Cancer Genome Atlas to infer immune and stromal scores with the 'Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data' (ESTIMATE) algorithm and identified immune-related differentially expressed genes (DEGs) between the high- and low-stromal/immune score groups. Next, all DEGs were subjected to univariate Cox regression and survival analyses to screen out prognostic biomarkers in the tumor microenvironment (TME), and were validated in the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to assess the level of tumor-infiltrating immune cells (TIICs) and immune functions, and GSEA was used to identified pathways altered by prognostic biomarkers. RESULTS: Survival analysis showed that LUAD in the high-immune and stromal score group had a better clinical prognosis. A total of 303 immune-related DEGs were detected. Univariate Cox regression and survival analyses revealed that P2Y purinoceptor 13 (P2RY13) was a favorable factor for the prognosis of LUAD. ssGSEA and Spearman correlation analysis demonstrated that P2RY13 was highly correlated with various TIICs and immune functions. Several immune-associated pathways were enriched between the high- and low-expression P2RY13 groups. CONCLUSION: P2RY13 may be a potential prognostic indicator and is highly associated with the TME in LUAD. However, further experimental studies are required to validate the present findings.

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.

Left atrial concomitant surgical ablation for treatment of atrial fibrillation in cardiac surgery: A meta-analysis of randomized controlled trials.

INTRODUCTION: Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery. METHODS: A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints. RESULTS: Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups. CONCLUSIONS: The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery.

[Corrigendum] Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line.

Mol Med Rep 12:[Related article:] 7971­7978, 2015; DOI: 10.3892/mmr.2015.4468 Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Fig. 3A. The images selected for the '72 h Blank' and the '72 h Mock' panels were inadvertently selected from the same original photograph. This error arose during the editing process of our paper with a professional English Editing Service, and our failure to notice the mismatching of the images during the final proofreading of the manuscript prior to submission. A corrected version of Fig. 3 is presented here (right), which includes the corrected images for the 72 h Blank' and the '72 h Mock' panels. This error did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused.

Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line.

Eukaryotic translation initiation factor 4E (eIF4E) was shown to be upregulated in malignant human tumors. To assess the effect of downregulation of eIF4E on the proliferation and invasiveness of a human lung adenocarcinoma cell line, a short hairpin (sh)RNA targeting eIF4E was constructed and transfected into A549 human lung adenocarcinoma cells. The expression of eIF4E was determined by reverse transcription­quantitative polymerase chain reaction and western blotting. Cell viability was assessed using a Cell Counting kit­8, and apoptosis levels and cell cycle distribution were assessed by flow cytometry. Invasiveness was assessed using Transwell chambers. Transfection of the A549 cells with eIF4E targeting shRNA reduced the mRNA and protein expression levels of eIF4E by >70% 48 and 72 h following transfection, and eIF4E targeting shRNA­transfected cells were significantly less viable compared with the cells transfected with scrambled shRNA. The rate of apoptosis was also significantly increased, significantly more cells were in the G0/G1 phase and fewer were in the S phase, indicating cell cycle arrest. The fraction of transfected cells migrating across Transwell inserts were also reduced. In conclusion, inhibition of eIF4E suppressed cell growth and invasion, induced apoptosis and cell cycle arrest, suggesting that eIF4E may be a potential therapeutic target in lung adenocarcinoma.

Modified McKeown minimally invasive esophagectomy for esophageal cancer: a 5-year retrospective study of 142 patients in a single institution.

BACKGROUND: To achieve decreased invasiveness and lower morbidity, minimally invasive esophagectomy (MIE) was introduced in 1997 for localized esophageal cancer. The combined thoracoscopic-laparoscopic esophagectomy (left neck anastomosis, defined as the McKeown MIE procedure) has been performed since 2007 at our institution. From 2007 to 2011, our institution subsequently evolved as a high-volume MIE center in China. We aim to share our experience with MIE, and have evaluated the outcomes of 142 patients. METHODS: We retrospectively reviewed 142 consecutive patients who had presented with esophageal cancer undergoing McKeown MIE from July 2007 to December 2011. The procedure, surgical outcomes, disease-free and overall survival of these cases were assessed. RESULTS: The average total procedure time was 270.5 ± 28.1 min. The median operation time for thoracoscopy was 81.5 ± 14.6 min and for laparoscopy was 63.8 ± 9.1 min. The average blood loss associated with thoracoscopy was 123.8 ± 39.2 ml, and for laparoscopic procedures was 49.9 ± 14.3 ml. The median number of lymph nodes retrieved was 22.8. The 30 day mortality rate was 0.7%. Major surgical complications occurred in 24.6% and major non-surgical complications occurred in 18.3% of these patients. The median DFS and OS were 36.0 ± 2.6 months and 43.0 ± 3.4 months respectively. CONCLUSIONS: Surgical and oncological outcomes following McKeown MIE for esophageal cancer were acceptable and comparable with those of open-McKeown esophagectomy. The procedure was both feasible and safe - properties that can be consolidated by experience.