Cholesterol-lowering drug pitavastatin targets lung cancer and angiogenesis via suppressing prenylation-dependent Ras/Raf/MEK and PI3K/Akt/mTOR signaling.

Therapeutic agents that target both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy, particularly in lung cancer due to the critical roles of angiogenesis during lung cancer progression and metastasis. In this work, we showed that pitavastatin, a novel cholesterol-lowering drug, potently inhibited lung cancer cells and angiogenesis. This was achieved by the induction of apoptosis and inhibition of proliferation of lung cancer cells and human lung tumor-associated endothelial cell. Pitavastatin was not only effective to chemo-sensitive but also chemo-resistant lung cancer cells. This was also consistent with the finding that pitavastatin significantly enhanced cisplatin's efficacy in lung cancer xenograft model without causing toxicity in mice. We further showed that pitavastatin inhibited lung tumor angiogenesis in vitro and in vivo through suppressing human lung tumor-associated endothelial cell migration and morphogenesis without affecting adhesion. Mechanistically, we showed that pitavastatin acted on lung cancer cells and human lung tumor-associated endothelial cell through suppressing prenylation-dependent Ras/Raf/MEK and PI3K/Akt/mTOR signaling. Our work is the first to demonstrate the inhibitory effects of pitavastatin on Ras-mediated signaling. Our findings provide pre-clinical evidence to repurpose pitavastatin for the treatment of lung cancer.

CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/ß-catenin signaling pathway.

Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783-3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/ß-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783-3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783-3p/DKK1 axis.

Comparing efficacy and safety of regorafenib versus pemetrexed in lung cancer: A preliminary clinical trial evaluating effect of inflammatory biomarkers on disease progression.

This pilot clinical trial was designed to compare the efficacy and safety of regorafenib versus pemetrexed in Chinese patients with early stage of lung cancer. Also, the effect of inflammatory biomarkers on disease progression among Lung cancer patients who received regorafenib versus pemetrexed was evaluated in the present study. The patients who were diagnosed with early stage of lung cancer were enrolled. The eligible participants were randomized to receive regorafenib 160 mg (orally once daily for the first 21 days of each 28-day cycle) plus BSC or pemetrexed 500 mg/m2 intravenously (Day 1 of each 21-day cycle in combination with cisplatin 75 mg/m2 i.v. beginning 30 minutes after pemetrexed administration) plus BSC in a 1:1 ratio. Efficacy measures such as overall survival, progression-free survival and overall response were assessed after regorafenib and pemetrexed treatment. Safety of after regorafenib and pemetrexed treatment was also assessed. Blood was collected into a test tube pre-washed with chilled EDTA tubes, and then centrifuged to collect plasma sample for estimation of inflammatory biomarkers of interest. Survival time in respect to disease progression was also assessed. Also, biomarker assessments were made at each visit, to see whether inflammatory biomarker has any specific role on survival or in predicting progression of lung cancer. The present study results show that the safety and efficacy profile of regorafenib and pemetrexed was found similar in Chinese patients with early stage lung cancer. In general, regorafenib and pemetrexed treatment was well tolerated in Chinese patients with early stage Lung cancer. The results of this pilot study showed that inflammatory biomarkers such as interleukin 6 and interleukin 17A play an important role predicting progression of early stage lung cancer among Chinese patients.

Fabrication of Coral-like Polyaniline/Continuously Reinforced Carbon Nanotube Woven Composite Films for Flexible High-Stability Supercapacitor Electrodes.

The electrochemical performance is significantly influenced by the structure and surface morphology of the electrode materials used in supercapacitors. Using the floating catalytic chemical vapor deposition (FCCVD) technique, a self-supporting, flexible layer of continuously reinforced carbon nanotube woven film (CNWF) was developed. Then, polyaniline (PANI) was formed in the conductive network of CNWF using cyclic voltammetry electrochemical polymerization (CVEP) in various aqueous electrolytes to produce a series of flexible CNWF/PANI composite films. The impacts of the CVEP period, electrolyte type, and electrolyte concentration on the surface morphology, doping degree, and hydrophilicity of CNWF/PANI composite films were thoroughly examined. The CNWF/PANI1-15C composite electrode, which was created using 15 cycles of CVEP in a solution of 1 M sodium bisulfate, displayed a distinctive coral-like PANI layer with a well-defined sharp nanoprotuberance structure, a 48% doping degree, and a quick reversible pseudocapacitive storage mechanism. At a current density of 1 A g-1, the energy density and specific capacitance reached 54.9 Wh kg-1 and 1098.0 F g-1, respectively, with a specific capacitance retention rate of 75.9% maintained at 10 A g-1. Both the specific capacitance and coulomb efficiency were maintained at 96.9% and more than 98.1% of their initial values after being subjected to 2000 cycles of galvanostatic charge and discharge, demonstrating excellent electrochemical cycling stability. The CNWF/PANI1-15C composite film, an ideal electrode material, offers a promising future in the field of flexible energy storage due to its exceptional mechanical properties (127.9 MPa tensile strength and 16.2% elongation at break).

A random forest algorithm predicting model combining intraoperative frozen section analysis and clinical features guides surgical strategy for peripheral solitary pulmonary nodules.

Background: Intraoperative frozen section (FS) analysis has been used to guide the extent of resection in patients with solitary pulmonary nodules (SPNs), but its accuracy varies greatly among different hospitals. Artificial intelligence (AI) and multidimensional data technology are developing rapidly these years, meanwhile, surgeons need better methods to guide the surgical strategy of SPNs. We established predicting models combining FS results with multidimensional perioperative clinical features using logistic regression analysis and the random forest (RF) algorithm to get more accurate extent of SPN resection. Methods: Patients with peripheral SPNs who underwent FS-guided surgical resection at the Shanghai Chest Hospital (January 2017-December 2018) were retrospectively examined (N=3,089). The accuracy of intraoperative FS-guided resection extent was analyzed and used as Model 1. The clinical features (sex, age, CT features, tumor markers, smoking history, lesion size and nodule location) of patients were collected, and Models 2 and 3 were established using logistic regression and RF algorithms to combine the FS with clinical features. We confirmed the performance of these models in an external validation cohort of 117 patients from Hwa Mei Hospital, University of Chinese Academy of Science (Ningbo No. 2 Hospital). We compared the effectiveness in classifying low/high-risk groups of SPN among them. Results: The accuracy of FS analysis was 61.3%. Model 3 exhibited the best diagnostic accuracy and had an area under the curve of 0.903 in n the internal validation cohort and 0.919 in the external validation cohort. The calibration plots and net reclassification index (NRI) of Model 3 also exhibited significantly better performance than the other models. Improved diagnostic accuracy was observed in in both internal and external validation cohort. Conclusions: Using an RF algorithm, clinical characteristics can be combined with intraoperative FS analysis to significantly improve intraoperative judgment accuracy for low- and high-risk tumors, and may serve as a reliable complementary method when FS evaluation is equivocal, improving the accuracy of the extent of surgical resection.

Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study.

Objective: To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC. Methods: This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results: Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events. Conclusion: Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies. Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT04411706.

circRNA hsa_circ_0018414 inhibits the progression of LUAD by sponging miR-6807-3p and upregulating DKK1.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with a high incidence and mortality all over the world. In recent years, circular RNAs (circRNAs) have been verified to be a novel subtype of noncoding RNAs that exert vital functions in various cancers. Our research was designed to investigate the role of circ_0018414 in LUAD. We first observed that circ_0018414 was downregulated in LUAD tissues and cells. Also, low expression of circ_0018414 predicted unfavorable prognosis of LUAD patients. Then, upregulation of circ_0018414 repressed cell proliferation and stemness, while promoting cell apoptosis, in LUAD. Moreover, circ_0018414 overexpression enhanced the expression of its host gene, dickkopf WNT signaling pathway inhibitor 1 (DKK1), therefore inactivating the Wnt/ß-catenin pathway. Additionally, circ_0018414 could sponge miR-6807-3p to protect DKK1 mRNA from miR-6807-3p-induced silencing, leading to DKK1 upregulation in LUAD cells. Finally, rescue assays proved that circ_0018414 inhibited the progression of LUAD via the miR-6807-3p/DKK1 axis-inactivated Wnt/ß-catenin pathway. The findings in our work indicated circ_0018414 as a tumor inhibitor in LUAD, which might provide a new perspective for LUAD treatment.

Continuously Reinforced Carbon Nanotube Film Sea-Cucumber-like Polyaniline Nanocomposites for Flexible Self-Supporting Energy-Storage Electrode Materials.

The charge storage mechanism and capacity of supercapacitors completely depend on the electrochemical and mechanical properties of electrode materials. Herein, continuously reinforced carbon nanotube film (CNTF), as the flexible support layer and the conductive skeleton, was prepared via the floating catalytic chemical vapor deposition (FCCVD) method. Furthermore, a series of novel flexible self-supporting CNTF/polyaniline (PANI) nanocomposite electrode materials were prepared by cyclic voltammetry electrochemical polymerization (CVEP), with aniline and mixed-acid-treated CNTF film. By controlling the different polymerization cycles, it was found that the growth model, morphology, apparent color, and loading amount of the PANI on the CNTF surface were different. The CNTF/PANI-15C composite electrode, prepared by 15 cycles of electrochemical polymerization, has a unique surface, with a "sea-cucumber-like" 3D nanoprotrusion structure and microporous channels formed via the stacking of the PANI nanowires. A CNTF/PANI-15C flexible electrode exhibited the highest specific capacitance, 903.6 F/g, and the highest energy density, 45.2 Wh/kg, at the current density of 1 A/g and the voltage window of 0 to 0.6 V. It could maintain 73.9% of the initial value at a high current density of 10 A/g. The excellent electrochemical cycle and structural stabilities were confirmed on the condition of the higher capacitance retention of 95.1% after 2000 cycles of galvanostatic charge/discharge, and on the almost unchanged electrochemical performances after 500 cycles of bending. The tensile strength of the composite electrode was 124.5 MPa, and the elongation at break was 18.9%.

Impact of Somatic Mutations in Non-Small-Cell Lung Cancer: A Retrospective Study of a Chinese Cohort.

BACKGROUND: Somatic mutations are important biomarkers for selecting an optimal targeted therapy and predicting outcomes for non-small-cell lung cancer (NSCLC) patients that are often detected from tissue samples. However, tissue samples are not always readily available from these patients. The exploration of using circulating tumor DNA (ctDNA) to identify somatic mutations offers an alternative source that should be explored. METHODS: In this retrospective study, we included 280 patients diagnosed with adenocarcinoma between 2017 and 2018 in a hospital in eastern China. Tissue or ctDNA was collected, and a wide spectrum of somatic mutations was analyzed by targeted next-generation sequencing platforms. Associations among the mutation status, biomarkers, screening methods, disease stages, and interaction with treatment with overall survival (OS) were investigated. RESULTS: We found that the EGFR L858R mutation was the most frequently identified mutation in adenocarcinoma in this population by both methods, followed by KRAS (p=3.7e-09), PIK3CA (p=5e-04), and HER2 mutations (p=6.3e-03). We observed that EGFR mutations were significantly mutually exclusive with KRAS, HER2, and MET. FGFR1 mutations were significantly more abundantly detected in the ctDNA group. We found an interaction effect between EGFR mutation and target therapies. The ability of the targeted therapy to improve OS in patients with a single EGFR mutation (HR=0.069, p=0.07) approached significance, but this was not the case for the patients with more than one EGFR mutation or without an EGFR mutation (HR=0.813, p=0.725). Furthermore, the effect of chemotherapy was more predominant in the EGFR group in comparison to the control group. CONCLUSION: These findings provide useful information on the distribution of somatic mutations via different screening methods and how this related to the optimal treatment selection in Chinese patients with NSCLC.

Knockdown of TOR signaling pathway regulator suppresses cell migration and invasion in non-small cell lung cancer via the regulation of epithelial-to-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is one of the most common cancer types worldwide. Previous studies have indicated that TOR signaling pathway regulator (TIPRL) is involved in the progression of NSCLC. However, the underlying mechanisms of the role of TIPRL in regulating NSCLC metastasis have remained largely elusive. In the present study, the expression pattern of TIPRL in NSCLC was analyzed using The Cancer Genome Atlas (TCGA) dataset. Furthermore, Kaplan-Meier curve analysis was performed to evaluate the prognostic value of TIPRL in NSCLC, using the Kaplan-Meier Plotter and TCGA datasets. Loss-of-function assays were performed to determine the effects of TIPRL on cell migration and invasion. The results suggested that TIPRL was upregulated in NSCLC and positively associated with an advanced Tumor-Node-Metastasis stage. A higher expression level of TIPRL was associated with shorter overall and disease-free survival times in patients with NSCLC. To the best of our knowledge, the present study was the first to report that TIPRL acts as a metastasis promoter in NSCLC. Silencing of TIPRL suppressed A549 cell migration and invasion. Mechanistically, the present study indicated that TIPRL knockdown significantly promoted epithelial-cadherin expression, whereas it suppressed twist and vimentin expression in A549 cells. In conclusion, the present analysis suggested that TIPRL may serve as a biomarker for the prognosis of NSCLC and as a future target for its treatment.

YRDC is upregulated in non-small cell lung cancer and promotes cell proliferation by decreasing cell apoptosis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality worldwide. yrdC N6-threonylcarbamoltransferase domain containing protein (YRDC) has been demonstrated to be involved in the formation of threonylcarbamoyladenosine in transfer ribonucleic acid. However, the molecular mechanisms underlying NSCLC progression remain largely unclear. The present study revealed that YRDC was upregulated in NSCLC samples compared with adjacent non-cancerous tissues by analyzing datasets obtained from the Gene Expression Omnibus and The Cancer Genome Atlas. Higher expression of YRDC was associated with overall survival time and disease-free survival time in patients with NSCLC, particularly in lung adenocarcinoma. Furthermore, knockdown of YRDC in NSCLS cell lines significantly suppressed cell growth and cell colony formation in vitro. Additionally, the results demonstrated that silencing of YRDC induced apoptosis of A549 cells. Then, the protein-protein interaction networks associated with yrdC N6-threonylcarbamoltransferase domain containing protein (YRDC) in NSCLC were subsequently constructed to investigate the potential molecular mechanism underlying the role of YRDC in NSCLC. The results revealed that YRDC was involved in the regulation of spliceosomes, ribosomes, the p53 signaling pathway, proteasomes, the cell cycle and DNA replication. The present study demonstrated that YRDC may serve as a novel biomarker for the prognosis prediction and treatment of NSCLC.

miR­671­3p is downregulated in non­small cell lung cancer and inhibits cancer progression by directly targeting CCND2.

MicroRNAs (miRNAs) are implicated in the development and progression of non­small cell lung cancer (NSCLC). A previous study suggested that miR­671­3p suppresses the development of breast cancer. However, the role of miR­671­3p in NSCLC remains largely unknown. In the present study, it was identified that miR­671­3p was significantly upregulated in NSCLC tissues compared with adjacent normal tissues by reverse transcription quantitative polymerase chain reaction (RT­qPCR). Similarly, decreased levels of miR­671­3p in NSCLC cell lines were observed compared with those in the non­tumorigenic human bronchial epithelial NL20 cell line. Cell Counting Kit­8 and Transwell invasion assays indicated that miR­671­3p overexpression suppressed the proliferation and invasion of A549 cells, and vice versa. Mechanistically, it was demonstrated that CCND2 was a direct target of miR­671­3p. RT­qPCR and western blot analysis indicated that miR­671­3p overexpression decreased the expression of CCND2 in A549 cells. Furthermore, rescue experiments demonstrated that the restoration of CCND2 may significantly reverse the suppressive roles of miR­671­3p overexpression on NSCLC cell proliferation and invasion. Taken together, the present study demonstrated that miR­671­3p exerted its tumor­suppressive roles via directly targeting CCND2 in NSCLC.

Adjuvant Chemotherapy Following Surgical Resection Improves Survival in Patients With Early Stage Small Cell Lung Cancer.

The purpose of this study was to determine the effects of resection coupled with standard chemotherapy on the survival prognosis of patients with early stage small cell lung carcinoma (SCLC). Patients (n = 110) with mediastinal lymph node-negative SCLC were enrolled in this study. The baseline clinical data of patients with surgery were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were measured by Kaplan-Meier and log-rank test analyses. Ninety-eight patients received mediastinoscopy biopsy, and pulmonary lobectomy or sublobar resection, and 67 patients underwent adjuvant chemotherapy after pulmonary lobectomy. Adjuvant chemotherapy after surgical intervention was associated with longer OS (median OS: 42.14 vs. 33.53 months, p = 0.01) and PFS (median PFS: 25.20 vs. 13.48 months, p = 0.000) compared to resection alone for all patients. Adjuvant chemotherapy was associated with improvement of survival for N1 patients with stage II (median OS: 36.42 vs. 26.68 months, p = 0.021). The median PFS was 19.02 m (16.08, 21.96) and 13.25 m (10.19, 16.30) (p = 0.031), respectively, for patients of N1 stage who received chemotherapy and those who did not. Cox regression analysis demonstrated that age, TNM stage (N stage, not T stage), and chemotherapy were independent risk factors that might affect overall survival in patients with mediastinal lymph node-negative SCLC. These findings suggest that the application of adjuvant chemotherapy following pulmonary lobectomy is associated with improvements of survival prognoses for patients with SCLC. The combination of surgical intervention with conventional therapy should be taken into consideration as a prospective multidisciplinary regimen for early stage SCLC.

CircRNA has_circ_0001946 promotes cell growth in lung adenocarcinoma by regulating miR-135a-5p/SIRT1 axis and activating Wnt/ß-catenin signaling pathway.

Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of human cancers. However, little is known about the biological role and mechanism of circRNAs in lung adenocarcinoma (LAC). In the present study, we applied microarray analysis to screen for LAC-specific circRNAs. Top ten upregulated circRNAs were chosen for qRT-PCR analysis. Among them, circ_0001946 was significantly overexpressed in both LAC tissues and cell lines. In addition, the expression level of circ_0001946 was positively correlated with TNM stage and tumor size. Using Kaplan-Meier analysis, we found that circ_0001946 expression was negatively related with the overall survival of LAC patients. Next, we treated LAC cells with circ_0001946-specific shRNAs and found that knockdown of circ_0001946 inhibited LAC cell growth in vitro and in vivo. Mechanism investigation revealed that circ_0001946 was located in the cytoplasm of LAC cells and acted as a molecular sponge of miR-135a-5p to upregulate Sirtuin 1 (SIRT1) expression. Rescue assays further validated the role of circ_0001946-miR-135a-5p-SIRT1 axis in LAC progression. Additionally, SIRT1 has been demonstrated to be a positive regulator of Wnt/ß-catenin signaling pathway. Western blot analysis revealed that circ_0001946 regulated SIRT1/Wnt/ß-catenin signaling pathway. In conclusion, our findings suggested that circ_0001946 might be a potential biomarker for the diagnosis or treatment of LAC.

[Correlation between Plasma D-dimer Count and Features of
Non-small Cell Lung Cancer].

BACKGROUND: More and more patients with small pulmonary nodules (SPN) can be found along with the developing of chest low-dose computed tomography (LDCT). With current examinations not all the SPN can be diagnosed to be benign or malignant and not all the malignant nodules can be diagnosed to be lymphatic metastasis. We need to study the correlation between plasma D-dimer count of patients before surgery with pathology features of non-small cell lung cancer (NSCLC). METHODS: The study comprised 567 highly suspected lung cancer patients. Preoperative plasma D-dimer were qualified, and the relationship between plasma D-dimer with pathology features including benign or malignant nodules, tumor size and involvement of lymph nodes was examined using Kruskal-Wallis test and Spearman correlation coefficients. RESULTS: The median plasma D-dimer values were statistically higher in NSCLC patients than in those who suffered from benign lung nodules (P<0.001). The median plasma D-dimer values in NSCLC patients with malignant lymph nodes were statistically higher than in those without malignant lymph nodes (P<0.001). An obvious relationship was observed between elevated D-dimer with number of malignant lymph nodes involvement and tumer size. An obvious relationship was observed between elevated D-dimer (>112.5 ng/mL) and malignant lymph node involvement in stage T1 lung cancer. CONCLUSIONS: The plasma D-dimer maybe useful for early diagnosis, staging and prognosis of the patients with NSCLC. The plasma D-dimer can be one of the indicator to identify what kind of patients need mediastinal lymph node cleaning.

[Risk Factors of Non-small Cell Lung Cancer with Bone Metastasis after Therapy].

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, patients with non-small cell lung cancer (NSCLC) usually have distant metastases, such as bone metastasis, brain metastasis, and lung metastasis. The purpose of this study was to explore the risk factors for bone metastasis in NSCLC patients. METHODS: A total of 176 cases of NSCLC were selected from May 2009 to May 2011, and patients were divided into two groups, namely the bone metastasis group and non-bone metastasis group. The general clinicopathological data of the two groups and analyzing the independent risk factors of bone metastasis were compared. RESULTS: In the general clinicopathological data of NSCLC patients. The thrombus or not and tumor-node-metastasis (TNM) stage were closely related to the occurrence of bone metastasis, and were statistically significant (all P<0.01). Prothrombin time, activated partial thromboplastin time, Fibrinogen, thrombin time, blood platelet, D-Dimer and alkaline phosphatase have significantly difference between the two groups (all P<0.05). Logistic regression analysis showed that fibrinogen, activated partial thromboplast in time, alkaline phosphatase, T4 phase, N3 phase and d-dimer were independent risk factors for bone metastasis in NSCLC patients. CONCLUSIONS: Fibrinogen, alkaline phosphatase, T3, N2 stage and D-Dimer is the independent risk factors of bone metastases in patients with NSCLC.
.

Efficacy of thoracoscopic surgery in the treatment of lung cancer in the perioperative period and its effects on serum D-dimer.

The aim of this study was to investigate the feasibility and safety of thoracoscopic surgery in the treatment of lung cancer and its effect on serum D-dimer. A total of 218 patients with lung cancer treated in the Department of Thoracic Surgery of Ningbo No. 2 Hospital from January 1, 2013 to December 31, 2016, were retrospectively analyzed. Of the 218 patients, 120 patients underwent thoracotomy (thoracotomy group) and 98 patients underwent thoracoscopic surgery (thoracoscopy group). The clinical efficacy in the perioperative period and serum D-dimer level were compared between the two groups. In the present study, the intraoperative blood loss, blood transfusion rate, postoperative hospital stay, thoracic drainage time and volume in the thoracoscopy group were significantly shorter or smaller than those in the thoracotomy group (P<0.05), but there was no statistically significant difference in the average operation time between the thoracoscopy and the thoracotomy group. The incidence rate from moderate to severe pains in incisions after operation, the use rate of analgesics and the average disappearance time of the pain in incisions in the thoracoscopy were lower than those in the thoracotomy group (P<0.05). The amount of serum D-dimer immediately after operation in the thoracotomy group was significantly increased compared with that before operation (P<0.05), but there was no significant increase in the thoracoscopy group. At 24 h after operation, the serum D-dimer level in the two groups was further increased (P<0.05), and the comparison between the two groups showed that the levels of serum D-dimer in the thoracoscopy group immediately and at 24 h after operation were significantly lower than those in the thoracotomy group (P<0.05). The incidence rate of postoperative complications in the thoracoscopy was lower than that in the thoracotomy group, but the difference was not statistically significant. Our results show that thoracoscopic surgery is feasible and safe in the treatment of lung cancer. Compared with the thoracotomy group, the intraoperative condition and postoperative recovery have obvious advantages. The postoperative blood of patients is hypercoagulable and D-dimer increased gradually after 24 h. The effect of thoracoscopic surgery on serum D-dimer is relatively less effective.

MicroRNA-215 suppresses the proliferation, migration and invasion of non-small cell lung carcinoma cells through the downregulation of matrix metalloproteinase-16 expression.

The present study investigated the expression of microRNA (miR)-215 in non-small cell lung carcinoma (NSCLC) at tissue and cellular levels, as well as its biological functions and mechanism of action. A total of 56 patients with NSCLC were included in the present study. NSCLC tissues and tumor-adjacent normal tissues were resected and collected. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-215. Following transfection with miR-215 mimics, A549 cell proliferation, migration and invasion were determined using a Cell Counting Kit-8 and Transwell assay. Western blotting was employed to measure the expression of matrix metalloproteinase (MMP)-16 protein. A dual-luciferase reporter assay was conducted to determine the existence of a direct interaction between miR-215 and the MMP-16 gene. Reduced expression of miR-215 in NSCLC was closely associated with lymphatic metastasis and TNM staging. Overexpression of miR-215 inhibited the proliferation of A549 cells in vitro. Upregulated expression of miR-215 inhibited the migration and invasion of A549 cells in vitro. miR-215 exerted its biological functions possibly by regulating the expression of MMP-16. Elevated expression of MMP-16 promoted the proliferation, migration and invasion of A549 cells. miR-215 regulated the proliferation, migration and invasion of A549 cells by binding with the seed 3'-untranslated region of MMP-16 mRNA. The present study demonstrates that reduced expression of miR-215 in NSCLC is negatively associated with lymphatic metastasis and TNM staging. In addition, miR-215 acts as a tumor suppressor gene by inhibiting the proliferation, migration and invasion of NSCLC cells via the downregulation of MMP-16 expression.