Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Clinical Study of Artificial Intelligence in Imaging Diagnosis of False Positive Lesions of Pulmonary Nodules.

OBJECTIVE: To determine the accuracy of diagnosis of pulmonary nodules using artificial intelligence method. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Thoracic Surgery, Jinan Central Hospital, Jinan, China, from January 2020 to May 2021. METHODOLOGY: An analysis of clinical characteristics exhibited by 32 patients initially diagnosed with malignant tumours through imaging (LDCT) and artificial intelligence (AI), was reclassified as having benign lesions following surgical intervention. Quantitative parameters were assessed, including CT mean value, kurtosis, skewness, solid ratio, and the ratio of length to short diameter, within a cohort of 32 benign patients juxtaposed with 58 patients diagnosed with lung cancer during the same time frame. The AI-derived parameters were subjected to Mann-Whitney U non-parametric test. RESULTS: A total of 32 benign pulmonary lesions were evaluated that were initially misdiagnosed as malignant prior to surgery. These lesions displayed an average length of (18.56 ± 12.16) mm, with the majority characterised as solid (68.8%). Notably, a substantial proportion of these lesions exhibited imaging features akin to malignant growths. The AI-derived quantitative parameters of the 32 benign cases and the 58 malignant cases revealed statistical significance in average CT value and solid ratio. However, statistical significance was not established for kurtosis, skewness, or the ratio of length to short diameter. The area under the Receiver Operating Characteristic (ROC) curve for average CT value and solid ratio stood at 0.71 and 0.705, respectively. CONCLUSION: Among the cases initially misdiagnosed as malignant yet subsequently identified as benign, a notable number of these instances were solid nodules, often resembling malignant lesions in imaging characteristics. There was moderate discriminatory capacity for average CT value and solid ratio, rendering them valuable tools for distinguishing between benign and malignant lesions within this particular cohort. This underscores their high diagnostic significance. KEY WORDS: Artificial intelligence, Benign lesions of lung, Lung cancer, Quantitative parameters, Postoperative.

Establishment and Validation of a Novel Nomogram for Predicting Distant Metastasis in Patients with Invasive Lung Adenocarcinoma.

OBJECTIVE: To establish and verify a nomogram for predicting distant metastasis in invasive lung adenocarcinoma (IAC). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Thoracic Surgery, Jinan Central Hospital, Jinan, China, from December 2021 to May 2022. METHODOLOGY: To create a nomogram, univariate and multivariate logistic regression analyses were used to identify the independent predictors of distant metastasis. The calibration, discrimination, and clinical performance of the nomogram were tested by calibration plots, area under receiver operating characteristic curve (AUC), and decision curve analysis (DCA). RESULTS: Age at diagnosis (<70 years), histological type (invasive mucinous adenocarcinoma), T stage, N stage, surgical approach, and lymph node dissection were independent predictors for the development of nomogram. Compared with the American Joint Committee on Cancer-8th edition staging system, AUC showed that this prediction model has a higher predictive performance (training set: 0.922 vs. 0.790; verification set: 0.919 vs. 0.779). In addition, the overall survival time (OS) of IAC patients was meaningfully different among the three groups of different risks stratified based on model score (p <0.001). CONCLUSION: The prediction model constructed according to factors such as histological type and surgical approach in this study can accurately predict distant metastasis in IAC patients and define high-risk patients according to nomogram score. KEY WORDS: Invasive adenocarcinoma IAC, Distant metastasis, Nomogram, Surveillance, Epidemiology and end results SEER.

Establishment and Evaluation of EGFR Mutation Prediction Model Based on Tumor Markers and CT Features in NSCLC.

Background: Lung cancer has become one of the leading causes of cancer deaths worldwide. EGFR gene mutation has been reported in up to 60% of Asian populations and is currently one of the main targets for genotype-targeted therapy for NSCLC. Objective: The objective is to determine if a complex model combining serum tumor makers and computed tomographic (CT) features can predict epidermal growth factor receptor (EGFR) mutation with higher accuracy. Material and Methods. Retrospective analysis of the data of patients diagnosed with in nonsmall cell lung cancer (NSCLC) by EGFR gene testing was carried out in the Department of Thoracic Surgery, Jinan Central Hospital. Multivariate logistic regression analysis was used to determine the independent predictors of EGFR mutations, and logistic regression prediction models were developed. The subject operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to assess the accuracy and clinical application of the EGFR mutation prediction model. Results: Logistic regression analysis identified the predictive factors of EGFR mutation including nonsmoking, high expression level of Carcinoembryonic Antigen (CEA), low expression level of cytokeratin 19 fragments (CYFRA21-1), and subsolid density containing ground-glass opacity (GGO) component. Using the results of multivariate logistic regression analysis, we built a statistically determined clinical prediction model. The AUC of the complex prediction model increased significantly from 0.735 to 0.813 (p = 0.014) when CT features are added and from 0.612 to 0.813 (p < 0.001) when serum variables are added. When P was 0.441, the sensitivity was 86.7% and the specificity was 65.8%. Conclusion: A complex model combining serum tumor makers and CT features is more accurate in predicting EGFR mutation status in NSCLC patients than using either serum variables or imaging features alone. Our finding for EGFR mutation is urgently needed and helpful in clinical practice.

Research progress on the occurrence and therapeutic mechanism of ferroptosis in NSCLC.

Ferroptosis refers to a novel way of cell death, inconsistent with the conventional concept of apoptosis and necrosis. It shows a close association with iron metabolism and oxidative damage, as marked by the significant increase of reactive oxygen species, the decreases of mitochondrial volume, and the thickening of membrane density. Recent studies confirmed that ferroptosis is closely associated with the occurrence, development, and therapy of the tumors. As impacted by the high levels of reactive oxygen species and lipid peroxides in lung cancer tissues, it is suggested that ferroptosis is more likely to occur in lung cancer tissues, which may act as a novel approach for non-small cell lung cancer (NSCLC) therapy. In the present study, the research achievements in recent years on the regulating mechanism of ferroptosis and its effect on the occurrence and the therapy of lung cancer are reviewed.

Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis.

Long non-coding RNAs (lncRNAs) are closely associated with the development of lung adenocarcinoma (LADC). The present study focused on the role of LINC00960 in LADC. miRNA and mRNA expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular functions were evaluated by MTT, colony formation, and Transwell assays, respectively. LINC00960 Luciferase and RNA pull-down assays were performed to clarify the interaction between miR-124a and LINC00960 or Recombinant Sphingosine Kinase 1 (SphK1). We observed that LINC00960 was overexpressed in LADC tumor tissues and cell lines. LINC00960 knockdown suppressed the proliferation, migration, and invasion of LADC cells. Moreover, LINC00960 sponged miR-124a to inhibit the SphK1/S1P pathway in LADC cells. LINC00960 knockdown markedly reduced the rate of tumor growth. The luciferase reporter assay results demonstrated an interaction between miR-124a and LINC00960 or SphK1. This interaction was confirmed using the RNA pull-down assay. In addition, miR-124a downregulation or SphK1 upregulation reversed the inhibitory effects of LINC00960 knockdown on cellular functions of LADC cells, suggesting that LINC00960 may be a potential therapeutic biomarker for LADC via the miR-124a/SphK1 axis. Accordingly, LINC00960 may be a potential therapeutic biomarker for LADC.

Correlation between Circulating Tumor Cells and Plasma D-dimer and Clinicopathological Characteristics of Patients with Non-small Cell Lung Cancer.

OBJECTIVE:  To study the relationship between circulating tumor cells (CTCs) and plasma D-dimer (D-D) and their correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China, from December 2015 to August 2019. METHODOLOGY: Seventy-five patients with NSCLC were selected as the research subjects. The contents of CTCs and D-D were determined and the results were analysed as per objective. Data was analysed quantitatively, using SPSS Version 24.0. RESULTS: Forty-five patients with NSCLC were positive for CTCs. The level of D-D in NSCLC patients was significantly increased. The D-D level in CTCs-positive patients was 0.79 (0.43-1.80) mg/L. The levels of CTCs and D-D in NSCLC patients were not affected by gender and pathological subtypes and other factors (p>0.05). CTCs and D-D in peripheral blood of NSCLC patients were significantly correlated with the total stage of lung cancer patients (p <0.05). CONCLUSION: The levels of CTCs and D-D in peripheral blood of NSCLC patients are significantly correlated with clinicopathological features, and the positive CTCs and high levels of D-D may indicate the late stage of the disease and poor prognosis, and there is a correlation between the two. The combined detection of the two is of great significance in predicting the progress and poor prognosis of NSCLC patients, and can guide the clinical diagnosis and treatment. Key Words: Non-small cell lung cancer (NSCLC), Circulating tumor cells (CTCs), D-dimer (D-D), Clinicopathologic features.

MicroRNA-363-3p inhibits tumor cell proliferation and invasion in oral squamous cell carcinoma cell lines by targeting SSFA2.

The aim of the present study was to evaluate the expression levels of microRNA (miR)-363-3p and its underlying physiological function in oral squamous cell carcinoma (OSCC). miR-363-3p expression levels were measured in OSCC cell lines using reverse transcription-quantitative PCR. The role of miR-363-3p in OSCC cells was examined using gain-of-function assays in vitro. Cell proliferation was assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assays and flow cytometry. Cell migration and invasion were evaluated in wound-healing and Transwell Matrigel assays. In addition, bioinformatics analysis predicted binding sites of miR-363-3p on sperm-specific antigen 2 (SSFA2). Luciferase reporter and RNA pull-down assays were conducted to test whether miR-363-3p interacted with SSFA2. miR-363-3p expression was downregulated in OSCC cell lines compared with that in the normal epithelial cell line (NHOK). Additionally, miR-363-3p overexpression suppressed OSCC cell proliferation, migration and invasion in vitro. SSFA2 was verified as a direct target of miR-363-3p, and SSFA2 overexpression partially counteracted the inhibitory effects of miR-363-3p on cell proliferation, migration and invasion in OSCC cell lines. Thus, miR-363-3p may serve as a tumor suppressor via targeting SSFA2 and may represent a potential therapeutic target for OSCC.

Application of Dexmedetomidine Sedation Combined With Suprascapular Nerve Block and Axillary Nerve Block in Shoulder Arthroscopy, A Randomized Single-Blind Study.

Objective: The aim of the present study was to evaluate the anesthetic and analgesic effects of dexmedetomidine combined with suprascapular nerve block and axillary nerve block in shoulder arthroscopy. Methods: A total of 60 patients were randomly divided into the experimental group (DEX group) and the control group (GA group) via a random number table method. Dexmedetomidine sedation combined with suprascapular nerve block and axillary nerve block was used in the DEX group, while general anesthesia with tracheal intubation combined with interscalene brachial plexus block was used in the GA group. The perioperative indexes, intraoperative hemodynamics, cerebral oxygen saturation, and postoperative pain score, as well as any complications, were compared between the two groups. Results: The anesthesia duration (p < 0.05) and postoperative monitoring time (p < 0.05) in the DEX group were significantly shorter than those in the GA group. At most time points during the anesthesia, the cerebral oxygen saturation (p < 0.05) and mean arterial pressure (p < 0.05) in the DEX group were significantly higher than those in the GA group. Additionally, the decrease in the cerebral oxygen saturation and mean arterial pressure in the GA group was significantly higher than that in the DEX group (p < 0.05). The pain score of DEX group 12 h after operation significantly lower than that in the GA group (p < 0.05), and the incidence of postoperative hypoxemia along with nausea and vomiting in the GA group was significantly higher than that in the DEX group (p < 0.05). Conclusion: Dexmedetomidine combined with suprascapular nerve block and axillary nerve block could reduce the incidence of hypoxemia, while the approach demonstrated better hemodynamic stability, fully ensured the cerebral blood perfusion, and exhibited better anesthetic and analgesic effects, meaning it could be safely and effectively applied in shoulder arthroscopy procedures.

Microwave ablation combined with chemotherapy improved progression free survival of IV stage lung adenocarcinoma patients compared with chemotherapy alone.

BACKGROUND: Microwave ablation (MWA) has recently become an established treatment option for topical therapy of lung cancer patients. In this study, we evaluated whether MWA combined with chemotherapy could improve progression-free survival (PFS) of patients with stage IV lung adenocarcinoma compared with chemotherapy alone. METHODS: A total of 49 patients were enrolled into the study; 21 patients accepted MWA therapy combined with chemotherapy, 28 patients accepted only chemotherapy. Enumeration data were analyzed using χ2 test or Fisher's exact probability test and univariate analysis was analyzed using Kaplan-Meier survival curves. Multivariate analysis was carried out with the Cox proportional hazard model. RESULTS: The treatment regimen was not correlated with clinical features of the patients, which included gender, age, smoking history, tumor site, tumor size and Eastern Cooperative Oncology Group (ECOG). The patients' 3-year overall survival (OS) was 12.5%, and median survival time was 19.3 months. The median PFS was 6.1 months and the 1-year PFS was 0.0%. The PFS was significantly associated with tumor size (P < 0.05), ECOG (P < 0.01) and treatment regimen (P < 0.01). The median time to local progression (TTLP) was 8.4 months and the 3-year TTLP was 2.0%. The TTLP was significantly associated with tumor size (P < 0.05) and treatment regimen (P < 0.01). Cox multivariate regression demonstrated that MWA combined with chemotherapy was the independent factor for both the PFS and TTLP. CONCLUSION: MWA, as a topical treatment method, when combined with chemotherapy improved the PFS and TTLP of patients with stage IV lung adenocarcinoma.

Clinical and prognostic significance of MUC1 expression in patients with esophageal squamous cell carcinoma after radical resection.

Background/Aim: To investigate the clinical and prognostic significance of MUC1 expression in patients with esophageal squamous cell carcinoma (ESCC) after radical resection. Materials and Methods: A total of 108 ESCC specimens were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1 at the mRNA level and were evaluated by immunohistochemistry (IHC) to detect MUC1 at the protein level. Results: MUC1 mRNA was found in 74 cases by RT-PCR and MUC1 protein expression was found by IHC in 70 cases. Both MUC1 mRNA and protein expression correlated with pT (<0.05), pN (P < 0.01), and pTNM (<0.01). The 5-year survival rates of the patients were 39.8%. In univariate analysis, the 5-year survival rate in the ESCC patients was significantly associated with pT (P < 0.01), pN (P < 0.01), pTNM stage (P < 0.01), and MUC1 mRNA and protein expression (P < 0.05). In multivariate analysis, pN and MUC1 expression were the independent relevant factors. Conclusion: MUC1 expression can become a useful marker to predict poor prognostic factors for 5-year survival rate in patients with ESCC after radical resection.

Clinical and prognostic significance of signal transducer and activator of transcription 3 and mucin 1 in patients with non-small cell lung cancer following surgery.

Signal transducer and activator of transcription 3 (STAT3) and mucin 1 (MUC1) are associated with development, progression and a poor prognosis in several types of cancer. The present study investigated the levels of STAT3 and MUC1 in patients with non-small cell lung cancer (NSCLC) following surgery. In total, 98 patients with NSCLC were enrolled into the study. STAT3, phosphorylated (p)-STAT3 and MUC1 expression in NSCLC specimens obtained from patients were investigated using immunohistochemical analysis. Enumeration results were analyzed using the χ2 test or Fisher's exact probability test. Spearman's rank correlation was used to analyze correlations between STAT3, p-STAT3 and MUC1 expression. Univariate analysis was conducted using the Kaplan-Meier estimator curve method and Cox regression multivariate analysis was performed in order to determine prognostic factors. Results demonstrated that STAT3 and p-STAT3 expression was identified in 82 and 51 patients, respectively. Furthermore, the expression of MUC1 was identified in 61/98 cases (62.2%) and STAT3 expression was significantly associated with pathological tumor-node-metastasis stage (pTNM; P<0.01). p-STAT3 expression was associated with pathological type (P<0.01), pathological lymph nodes (pN; P<0.01) and pTNM (P<0.05). MUC1 expression was associated with pathological type (P<0.05), pathological tumor pT (P<0.05), pN (P<0.01) and pTNM (P<0.01). STAT3 expression was positively associated with p-STAT3 expression (P<0.05) and p-STAT3 expression was positively associated with MUC1 expression (P<0.01). Overall, the results identified that the 3-year survival rate was 56.1% and was significantly associated with the degree of differentiation (P<0.05), pT (P<0.01), pN (P<0.01), pTNM stage (P<0.01), p-STAT3 expression (P<0.01) and MUC1 expression (P<0.05). Results obtained from the Cox multivariate regression analysis demonstrated that pN and p-STAT3 expression were independent factors associated with the 3-year survival rate.

Low expression of miR-1469 predicts disease progression and unfavorable post-surgical clinical outcomes in patients with esophageal squamous cell cancer.

Recent studies have demonstrated that deregulated microRNA (miRNA/miR) expression has a profound impact on biological and pathological processes; abnormal miR-1469 expression was detected in several human malignancies. In the present study, the clinicopathological and prognostic significance of miR-1469 was assessed in 129 patients with esophageal squamous cell cancer (ESCC) who successfully underwent esophagectomy and esophagogastrostomy. Low miR-1469 expression was identified to be significantly associated with tumor invasion depth (P=0.026), lymph node metastasis status (P<0.001) and pathological tumor stage (P<0.001). Survival analysis demonstrated that patients with low miR-1469 expression had significantly poorer disease-free survival (DFS) (18.2 vs. 43.2%; P=0.004) and overall survival (29.1 vs. 47.3%; P=0.029) 5 years following surgery compared with patients with high miR-1469 expression. Univariate survival analysis demonstrated that low miR-1469 expression significantly predicted unfavorable 5-year DFS among patients with N1-3 disease (7.1 vs. 31.8%; P=0.043). The results from the present study indicate that miR-1469 expression could be used in the clinic to predict ESCC progression and prognosis. This will aid in the identification of high-risk patients with ESCC that require more aggressive therapeutic interventions.

Mucin 1 expression correlates with metastatic recurrence in postoperative patients with esophageal squamous cell cancer.

Mucin1 (MUC1) expression correlates with invasion and metastasis and poor survival in some cancers. The purpose of the study was to investigate the clinical significance of MUC1 expression and the risk of tumor metastatic recurrence in patients with esophageal squamous cell cancer (ESCC) after curative resection. A total of 108 ESCC patients were enrolled in this study. MUC1 expression was detected in ESCC tissues from 70 patients by immunohistochemistry (IHC). The expression of MUC1 in the cancerous tissue group was significantly higher than that in the paracancerous normal tissue group (65.4%:10.0%, p < 0.01). MUC1 expression correlated with pT (< 0.05), pN (p < 0.01) and pTNM stage (< 0.01). The 5-year survival rate of the patients was 39.8%. The 5-year tumor metastatic recurrence rate of the patients was 74.1%, and it was associated with pT (p < 0.01), pN (p < 0.01), pTNM stage (p < 0.01) and MUC1 expression (p < 0.01). Multivariate analysis confirmed that pN and MUC1 expression were independent predictive factors. In conclusion, MUC1 expression correlates with tumor metastatic recurrence in postoperative ESCC patients.

The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2.

In recent years, microRNAs, also called as miRNAs, play an important role in carcinogenesis, and the dysregulation of miRNAs is closely associated with cancer progression. Till now, little has been known about the role of miRNA-146a in the esophageal squamous cell carcinomas (ESCC). In the present study, we used in vitro assays to investigate the mechanisms of miRNA-146a in ESCC cell lines and 60 ESCC tissues. Here, we found that miRNA-146a expression is downregulated in both ESCC cell lines and tissues and obviously associated with pathological indicators, such as metastasis and stage of ESCC. In addition, the overexpression of miRNA-146a suppressed EC109 and TE8 cell proliferation and invasion. Meanwhile, miRNA-146a overexpression extremely inhibited the protein expression of insulin receptor substrate 2 (IRS2). Notably, the enforced expression of IRS2 in EC109 cells with miRNA-146a overexpression attenuated the inhibitory effects of miRNA-146a. In conclusion, our findings suggest that miRNA-146a may function as a useful clinical tool in the treatment and diagnosis of ESCC, and its overexpression suppressed cell growth through inhibition of IRS2. Thus, miRNA-146a pathway may be recommended as potential makers for drug design.

Sphingosine kinase 1 enhances the invasion and migration of non-small cell lung cancer cells via the AKT pathway.

Sphingosine kinase 1 (SphK1) has been shown to play an important role in the progression of a number of human cancers. It has been reported that the expression of SphK1 is greatly elevated in non-small cell lung cancer (NSCLC) tissues. However, its role and underlying mechanisms in NSCLC have not been fully elucidated. In the present study, we found that SphK1 was highly expressed in NSCLC cells. Overexpression of SphK1 promoted the invasion and migration of NSCLC cells, while knockdown of SphK1 suppressed the invasion and migration. Furthermore, we demonstrated that SphK1 decreased the protein level of E-cadherin, yet increased the protein level of Snail. In addition, SphK1 was able to stimulate the activation of AKT. Inhibition of the AKT pathway attenuated the biological functions of NSCLC cells induced by overexpression of SphK1. Taken together, our findings suggest that SphK1 can enhance the invasion and migration of NSCLC cells via activation of the AKT pathway and regulation of E-cadherin and Snail expression. Thus, SphK1 could be a potential target for the detection and treatment of NSCLC.

Down-regulation of heparanase leads to the inhibition of invasion and proliferation of A549 cells in vitro and in vivo.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.