Yunsong Li

Research on the Relationship Between Serum Levels of Inflammatory Cytokines and Non-small Cell Lung Cancer

AIMS This study was conducted to evaluate the levels of TNF-α, IL-6, IL-8 and VEGF in serum of patients with non- small cell lung cancer, for assessing their possible diagnostic and prognostic roles. METHODS We enrolled 48 patients newly diagnosed with non-small cell lung cancer and 40 healthy controls. TNF- α, IL-6 and IL-8 levels were measured in the serum of all the subjects with specific radioimmunoassay kits, while EGF was analyzed by sandwich enzyme immunoassay techniques. RESULTS A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-α, IL-6, IL-8 and VEGF in serum. Moreover, TNF-α, IL-8 and VEGF levels were higher in patients with advanced stages compared to early stages. In addition, higher serum levels of TNF-α, IL-6, IL-8 and VEGF were found in smokers than in non-smokers, both in patients and controls. CONCLUSION Serum levels of TNF-α, IL-6, IL-8 and VEGF were all elevated in lung cancer patients, suggesting that inflammatory cytokines could be jointly used as a screening tool. Though TNF-α, IL-8 and VEGF levels were related to advanced disease, long-term survival studies of NSCLC patients should be performed to confirm whether they can act as biomarkers of advanced disease. In addition, smoking would be an important contributor to the processes of inflammation and lung cancer.

Correlation Between Expression of Cell Adhesion Molecules CD 44 v6 and E-cadherin and Lymphatic Metastasis in Non-small Cell Lung Cancer

Objective: To explore the relationship between expressions of cell adhesion molecules CD44 v6 and E-cadherin (E-cad) and lymphatic metastasis in non-small cell lung cancer (NSCLC). Materials and Methods: Eighty- seven tissue samples obtained from patients with primary NSCLC were collected in our hospital from Dec., 2007 to Dec., 2012, and the expressions of CD44 v6 and E-cad gene proteins in these samples were detected by immunohistochemical method. Results: In the tissue without lymphatic metastasis, the positive expression rate of CD44 v6 was significantly lower, whereas the normal expression rate of E-cad was notably higher than that with lymphatic metastasis (55.6% vs. 78.4%, 47.2% vs. 21.6%), and both differences had statistical significance (P<0.05). Besides, CD44 v6 and E-cad expressions had a significant correlation in the NSCLC tissue with lymphatic metastasis (P<0.05). Conclusions: The positive expression of CD44 v6 and abnormal expression of E-cad may play a very important role in promoting lymphatic metastasis of NSCLC, with synergistic effect. Hence, detection of CD44 v6 and E-cad expressions is conductive to judging the lymphatic metastasis in NSCLC.

Interleukin-8 -251A/T gene polymorphism and lung cancer susceptibility: a meta-analysis

Many studies have examined the association between the interleukin‐8 ‐251T/A (rs4073) gene polymorphism and lung cancer risk in various populations, but the results have been inconsistent. In this meta‐analysis, PubMed was searched for case–control studies published through 01 December 2013. The data were extracted, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. We assessed six published studies on the association between the interleukin‐8 ‐251T/A polymorphism and lung cancer risk. The included studies yielded a total of 3265 lung cancer cases and 3607 controls. For the homozygous A/A and A allele carriers (T/A + A/A), the pooled ORs for all studies combining 3265 cases and 3607 controls were 1.03 (95% CI = 0.92–1.14; P = 0.235 for heterogeneity) and 1.07 (95% CI = 0.96–1.19; P = 0.245 for heterogeneity) when compared with the homozygous wild‐type genotype (T/T). When the analysis was stratified by ethnicity, significant risks were found among Asians for both the A allele carriers and the homozygous A/A individuals. However, no significant associations were found in non‐Asian populations using any of the genetic models. This meta‐analysis suggests that the interleukin‐8 ‐251A allele confer an increased risk for the development of lung cancer among Asians.

Sleeve lobectomy by video-assisted thoracic surgery versus thoracotomy for non-small cell lung cancer

BackgroundBoth video-assisted thoracic surgery (VATS) and thoracotomy are used for sleeve lobectomy for patients with non-small cell lung cancer (NSCLC). This retrospective study aimed to assess the safety and efficacy of VATS sleeve lobectomy for NSCLC patients.MethodsBetween May 2009 and May 2013, 51 sleeve lobectomies (10 by VATS and 41 by thoracotomy) were performed for patients with NSCLC. Operative characteristics and postoperative course were compared between two groups.ResultsPatient demographics were similar between the two groups. Thoracotomy patients had larger tumors compared with VATS patients (p = 0.02). VATS patients had a longer operating time (p < 0.001) but a shorter length of postoperative hospital stay (p = 0.009). The two groups did not differ in pathologic stage, histologic results, blood loss, ICU stay, amount of chest drainage, duration of chest drainage, numbers and distributions of dissected lymph nodes and the occurrence of complications. There were no perioperative deaths in the VATS group, whereas there was one death (2.4 %) in the thoracotomy group. There were no conversions to thoracotomy in the VATS group. The overall median survival between the two groups was similar (3.2 years VATS versus 3.2 years thoracotomy, log-rank p = 0.58).ConclusionsVATS sleeve lobectomy for the treatment of NSCLC is technically feasible and safe and is associated with comparable complication rates and survival compared with thoracotomy approach, but it deserves further investigation in large series.

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

The purpose of this study was to figure out the effect of ciRS‐7/miR‐7/NF‐κB axis on the development of non‐small cell lung cancer (NSCLC). In response, the expressions of ciRS‐7, miR‐7 and NF‐κB subunit (ie RELA) within NSCLC tissues and cell lines were determined with real‐time polymerase chain reaction (RT‐PCR) and Western blot. Moreover, the NSCLC cells were transfected with pcDNA3‐ciRS‐7‐ir, pcDNA3‐ciRS‐7, miR‐NC and miR‐7 mimic. Furthermore, the targeted relationships between ciRS‐7 and miR‐7, as well as between miR‐7 and RELA, were confirmed by luciferase reporter assay. The proliferation, migration and apoptosis of NSCLC cells were, successively, measured using CCK‐8 assay, wound‐healing assay and flow cytometry test. Consequently, ciRS‐7, miR‐7, histopathological grade, lymph node metastasis and histopathological stage could independently predict the prognosis of patients with NSCLC (all P < .05). Moreover, remarkably up‐regulated ciRS‐7 and RELA expressions, as along with down‐regulated miR‐7 expressions, were found within NSCLC tissues and cells in comparison with normal ones (P < .05). Besides, overexpressed ciRS‐7 and underexpressed miR‐7 were correlated with increased proliferation, migration and invasion, yet reduced apoptosis rate of NSCLC cells (P < .05). More than that, ciRS‐7 specifically targeted miR‐7 to reduce its expressions (P < .05). Ultimately, the NSCLC cells within miR‐7 + RELA group were observed with superior proliferative, migratory and invasive capabilities than those within miR‐7 group (P < .05), and RELA expression was also significantly modified by both ciRS‐7 and miR‐7 (P < .05). In conclusion, the ciRS‐7/miR‐7/NF‐kB axis could exert pronounced impacts on the proliferation, migration, invasion and apoptosis of NSCLC cells.

Surgical treatment for pulmonary tuberculosis: is video-assisted thoracic surgery "better" than thoracotomy?

OBJECTIVE To compare video-assisted thoracoscopic surgery (VATS) lobectomy and conventional open lobectomy in patients with pulmonary tuberculosis (TB) who require surgery. METHODS Forty patients with pulmonary TB who required lobectomy were randomized to receive either VATS or open lobectomy. Patient demographic, pulmonary function, operative, and postoperative data were compared between the groups. RESULTS There were 20 patients who received VATS lobectomy (median age 31.5 years, range 19-67 years) and 20 that received open lobectomy (median age 33.5 years, range 16-60 years). The two groups were similar with respect to gender, age and pulmonary function (all, P>0.05). Lobectomy was completed by VATS in 19 of 20 patients (95%), and by thoracoscope-assisted mini-incision lobectomy in 1 patient. The median intraoperative blood loss was 345 mL (range, 100-800 mL), and the median duration of pleural cavity closed drainage was 5 days (range, 3-7 days). All open lobectomies were completed successfully, and the median intraoperative blood loss was 445 mL (range, 150-950 mL) and the median duration of pleural cavity closed drainage was 5 days (range, 3-9 days). No statistically significant differences were found between the groups with respect to operation completion rates, type of lung resection, intraoperative blood loss, closed pleural drainage duration and volume of postoperative chest drainage. The operation time, number of postoperative complications, postoperative pain index at 24 hours after surgery and postoperative hospital stay were all significantly less in the VATS group. With a median follow-up duration of 14 months (range, 8-18 months) no positive sputum examination results were found in either group. CONCLUSIONS VATS lobectomy is an effective and minimally invasive method for treating patients with pulmonary TB.

Exploratory study on the correlation between 14 lung cancer-related gene expression and specific clinical characteristics of NSCLC patients

Personalized medicine has become essential in the treatment of lung cancer. However, the lung cancer-related gene expression profiles in non-small cell lung cancer (NSCLC) patients have not been elucidated. In this study, the correlation between gene expression profiles and clinicopathological characteristics was investigated in NSCLC patients. A total of 95 patients were enrolled in this study. The mRNA expression levels of 14 genes were assessed by multiplex branched DNA liquidchip (MBL) technology and data on 9 clinicopathological characteristics of patients were collected simultaneously. The correlation between gene expression and clinicopathological characteristics was investigated. Out of the 9 clinicopathological parameters, 6 were associated with several of the 14 genes analyzed. Patient gender was associated with TYMS and TOP2A. Clinical stage was associated with VEGFR2, KIT and HER2. There was weak correlation between primary tumor size of ≤3 cm and the expression level of KIT. The mRNA expression levels of VEGFR2 and HER2 correlated with distant metastasis. BRCA1, TYMS, TOP2A and HER2 were associated with histological type. Smoking correlated with higher expression levels of BRCA1, TYMS and TOP2A and lower expression levels of PDGFRβ. The results were suggestive of correlation between the clinicopathological parameters of the NSCLC patients and the mRNA expression levels of certain lung cancer-related genes, including BRCA1, TYMS, TOP2A, PDGFRβ, VEGFR2, KIT and HER2.

Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients

We tested the hypothesis that circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in resected non-small cell lung cancer (NSCLC) patients. CTCs were separated from blood using magnetic beads coated with antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic-activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The association between CTCs and prognosis in these patients was evaluated after a 5-year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that the CTC count in PPB or IPVB was an independent risk factor for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of patients had a shorter median TFS (22 months vs. >60.0 months, p < 0.0012) and shorter OS (27 months vs. >60 months, p < 0.0015). The number of CTCs counted in PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC patients.

Long Noncoding RNA LINC00472 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Cells via Regulating miR-24-3p/DEDD

Objective: We aimed to detect the role of LINC00472 via regulating miR-24-3p and death effector domain-containing DNA-binding protein in lung adenocarcinoma. Methods: Long noncoding RNA, microRNA, and messenger RNA levels were determined using reverse transcription quantitative polymerase chain reaction. The expression of death effector domain-containing DNA-binding protein was determined using Western blot assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were conducted to explore the proliferation of cells. The cell apoptosis was tested by flow cytometry assay. Target relationships between miR-24-3p, death effector domain-containing DNA-binding protein, and LINC00472 were validated by dual-luciferase reporter gene assay. Results: LINC00472 and death effector domain-containing DNA-binding protein were found to be underexpressed, whereas miR-24-3p was found overexpressed in lung adenocarcinoma cell lines and tissues. Both LINC00472 and death effector domain-containing DNA-binding protein can bind to miR-24-3p. Overexpression of LINC00472 led to higher death effector domain-containing DNA-binding protein level, demoting cell proliferation while promoting apoptosis. Overexpression of miR-24-3p reduced death effector domain-containing DNA-binding protein level, which facilitated cell proliferation and inhibited cell apoptosis, as well as to some extent restrained the effects of LINC00472. The high expression of miR-24-3p in tumor cells was negatively related to LINC00472 and death effector domain-containing DNA-binding protein, whereas the expression of LINC00472 and that of death effector domain-containing DNA-binding protein were positively correlated. Conclusion: Our findings suggested that LINC00472 contributed to the increase in lung adenocarcinoma cell apoptosis and the inhibition of proliferation via regulating miR-24-3p/DEDD, which might provide a novel insight into potential therapeutic approach for lung adenocarcinoma.

Methylation of CLEC14A is associated with its expression and lung adenocarcinoma progression: SU et al.

Our main objective is probing the effect of methylation of CLEC14A on its expression and lung adenocarcinoma (LUAD) progression. Microarray analysis was utilized to screen out differentially downregulated genes with hypermethylation in LUAD tissues. The CLEC14A expression level was measured by western blot analysis and qRT‐PCR. Methylation‐specific‐PCR was performed to evaluate methylation status of CLEC14A. The 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromid (MTT) assay was used to check the relation between CLEC14A expression and cell proliferation. Cell cycle, cell apoptosis, migration, and invasion were respectively detected by the flow cytometry assay, wound healing assay, and transwell assay. Tumor xenograft models were established for investigating the effect of CLEC14A on tumor formation. CLEC14A expression in LUAD tissues was impaired compared with that in adjacent tissues, and CLEC14A promoter was highly methylated in LUAD. Overexpressing CLEC14A or inhibiting the methylation level of CLEC14A in A549 and LTEP‐a‐2 cells impeded the duplication of LUAD cells, promoted apoptosis, attenuated cell migration, and invasion ability, and arrested cell cycle at the G0/G1 phase. Overexpression of CLEC14A inhibited tumorigenesis of LUAD cells in nude mice. The promoter of CLEC14A is methylated in LUAD, leading to downregulation of CLEC14A in LUAD. CLEC14A acts as an antitumor role in LUAD by suppressing cell proliferation, migration, invasion, promoting cell apoptosis, and reducing tumorigenicity in nude mice. Thus, the inhibition of CLEC14A methylation is a novel strategy for the clinic treatment of LUAD.