Serum lemur tyrosine kinase-3: a novel biomarker for screening primary non-small cell lung cancer and predicting cancer progression

Purpose: We aimed to determine the expression level of serum soluble lemur tyrosine kinase-3 (sLMTK3) in human non-small cell lung cancer (NSCLC), and to examine whether the s sLMTK3 level could be used as a biomarker to screen primary NSCLC and to predict lung cancer progression. Methods: Serum levels of sLMTK3 in 67 patients with primary NSCLC, 28 patients with lung benign lesion, and 53 healthy volunteers were measured by sandwich ELISA. LMTK3 protein expression in NSCLC tissues and normal lung tissues was also detected by using immunohistochemical staining. Receiver operating characteristic (ROC) curve was selected to evaluate the sensitivity and the specificity of serum sLMTK3 level. Results: The mean concentration of sLMTK3 in NSCLC group was significantly higher than in the lung benign lesion group (P < 0.001) and the healthy control group (P < 0.001). Higher sLMTK3 level was correlated with age (P = 0.013), tumor-node-metastasis (TNM) stage (P < 0.001), and lymph node metastasis (P < 0.001) of NSCLC. In contrast to the normal lung tissues, increased LMTK3 expression was found in the NSCLC tissues, and was mainly located on the cytoplasm and the nuclei of cancer cells. For separating NSCLC from control group, the corresponding areas under the ROC curve (AUC) were 0.947 for sLMTK3 and 0.804 for CEA. With cutoffs of 10.05 ng/ml for sLMTK3 and 5.0 ng/ml for CEA respectively, the sensitivity and the specificity of sLMTK3 and CEA were, 80.60% and 97.53%, 35.82% and 96.30%, respectively, indicating better diagnostic value of sLMTK3. Conclusions: The sLMTK3 level was significantly increased in human NSCLC, and could be used as a potential and valuable biomarker for screening primary NSCLC and for predicting the progression of patients with this malignancy.     

Expression of IRAK1 in lung cancer tissues and its clinicopathological significance: a microarray study

The interleukin-1 receptor associated kinases 1 (IRAK1) is a down stream effector molecule of the toll like receptor (TLR) signaling pathway, which is involved in inflammation, autoimmunity and cancer. However, the role of IRAK1 in lung cancer remains unclarified. Herein, we investigated the protein expression and the clinicopathological significance of IRAK1 in 3 formalin-fixed paraffin-embedded lung cancer tissue microarrays by using immunohistochemistry, which included 365 tumor and 30 normal lung tissues. We found that the expression of IRAK1 in lung cancer was significantly higher compared with that in normal lung tissues (P=0.002). Receiver operating characteristic (ROC) curves were generated to evaluate the power of IRAK1 to distinguish lung cancer from non-cancerous lung tissue. The area under curve (AUC) of ROC of IRAK1 was 0.643 (95% CI 0.550~0.735, P=0.009). Additionally, IRAK1 expression was related to clinical TNM stage (r=0.241, P < 0.001), lymph node metastasis (r=0.279, P < 0.001) and tumor size (r=0.299, P < 0.001) in lung cancer. In the subgroup of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the positive rates of IRAK1 were both higher than that in the normal lung tissues (P=0.003, P=0.002, respectively). Further spearman analysis showed that IRAK1 protein in NSCLC was positive correlated with clinical TNM stage (r=0.222, P < 0.001), lymph node metastasis (r=0.277, P < 0.001), tumor size (r=0.292, P < 0.001) and distal metastasis (r=0.110, P=0.043). In conclusion, the expression of IRAK1 protein might be valuable in identifying patients with increased risks of lung cancer and might act as a target for diagnosis and gene therapy for lung cancer.     

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival

Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.     

Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer

Introduction: MicroRNA-124 (miR-124) has been proven dysregulated in several human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to investigate the clinical significance of miR-124 expression in NSCLC. Methods: Expression levels of miR-124 in 92 pairs of NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: miR-124 expression level was significantly lower in NSCLC tissues compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124 expression group was significantly shorter than that of high miR-124 expression group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was also significantly shorter than that of high miR-124 expression group (P < 0.05). In a multivariate Cox model, we found that miR-124 expression was an independent prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05). Conclusions: Our results offer the convincing evidence that miR-124 may play key roles in the progression of lung cancer and that the down-regulated expression of miR-124 may be independently associated with shorter OS and DFS of patients, suggesting that miR-124 might be a potential marker for further risk stratification in the treatment of lung cancer.     

Homocysteine,endothelin-1 and nitric oxide in patients with hypertensive disorders complicating pregnancy

Objective: To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP. Methods: Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay. Results: Serum Hcy and ET-1 in HDCP group were significantly higher as compared to control group (P<0.05). Level of serum NO in HDCP group was significantly lower than in the control group (P<0.05). Level of serum Hcy and ET-1 in mild and severe preeclampsia group were significantly higher as compared to control group, respectively (P<0.05). Level of serum NO in mild and severe preeclampsia group were significantly lower than in the control group’ respectively (P<0.05). Level of serum Hcy and ET-1 in severe preeclampsia group were significantly higher as compared to mild preclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05). Conclusion: Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP.     

Significance of plasma hepatocyte growth factor in diagnosis of benign and malignant solitary pulmonary nodules

Purpose: We aimed to figure out the difference of serum hepatocyte growth factor (S-HGF) level between benign and malignant solitary pulmonary nodules (SPNs) patients. Methods: The study comprised 42 serum samples from SPNs patients and 10 serum samples of healthy donors. The HGF level was measured by the commercially enzyme-linked immunosorbent assay (ELISA) kit. Results: By statistical analysis, the S-HGF levels of the malignant SPNs patients were significantly higher than that of control group (P < 0.05). Moreover, the levels of S-HGF in malignant group were also significantly higher than that in benign group (P < 0.05), while there was no significant difference between the benign and control group (P > 0.05). The levels of S-HGF were also shown no statistically significant difference (P > 0.05) in different pathologic types of lung cancer patients. In addition, the incidence of malignant SPNs increased when the S-HGF level ≥ 250 pg/ml. Conclusion: The detection of S-HGF level may be a new detection method used for the rapid diagnosis of benign and malignant SPNs.     

The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study

Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer.Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8.Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively)Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.     

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score

BackgroundThis study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer.MethodsThis retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes.ResultsOf the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001).ConclusionStratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.     

Liquid-based cytological test of samples obtained by catheter aspiration is applicable for the bronchoscopic confirmation of pulmonary malignant tumors

The aim of the present study is to confirm the value of electronic bronchoscopy-aided catheter aspiration technique with liquid-based cytological test in the diagnosis of bronchogenic carcinoma. A total of 815 patients of lung cancer were evaluated by bronchoscopy between February 2011 and June 2012. Catheter aspiration technique and forceps biopsy during bronchoscopy were employed to obtain adequate tissue specimens. Liquid-based cytological test and conventional smears for catheter aspiration were used for cytological detection of the tumors. For all cytological specimens, slide preparations with LCT and CS were reviewed by two senior pathologists, who were blinded to patient medical history. Complications related to electronic bronchoscopy, such as bleeding, were clinically judged as light, moderate or severe by the needs for clinical interventions. The diagnostic yield of catheter aspiration in endobronchial visible lesions (tumor, infiltrative and necrotic lesions) was 94.6% (success rates concerning malignancy), which was slightly higher than that of the forceps biopsy (91.4%, P < 0.05). The diagnostic yield of catheter aspiration in endobronchial invisible lesions (normal, compressive and nonspecific lesions) was 82.8%, which was significantly higher than that of the forceps biopsy (51.4%, P < 0.01). The combination of the forceps biopsy with the cytological analysis of the catheter aspiration increased the diagnostic sensitivity in both lesion types (P < 0.05). For catheter aspiration, the positive rate of lung cancer by liquid-based cytological test was superior to that by conventional smears (P < 0.05). The catheter aspiration is a sampling technique that produces higher diagnostic rate for lung cancers compared with forceps biopsy. Liquid-based cytological test is routinely applicable for the diagnosis of lung cancer using samples collected through electronic bronchoscopy.     

Aberrant expression of Per1, Per2 and Per3 and their prognostic relevance in non-small cell lung cancer

The objective of the current study was to investigate the expression pattern and clinicopathological significance of Period1 (Per1), Period2 (Per2) and Period3 (Per3) in patients with non-small cell lung cancer (NSCLC). In 130 archived NSCLC tissues, the positive rate of Per1 (86/130, 66.2%), Per2 (77/130, 59.2%) and Per3 (82/130, 63.1%) were reduced in human lung cancer samples compared with adjacent normal lung tissues (Per1, 119/130, 91.5%; Per2, 115/130, 88.5%; Per3, 121/130, 93.1%), as measured by immunohistochemical staining. Loss of Per1 was correlated with poor differentiation (P < 0.001), tumor status (P=0.04), high p-TNM stage (P < 0.001) and lymph node metastasis (P=0.045). The similar tendencies were also found in the correlation of the expression of Per2 and Per3 with clinicopathological factors. In addition, a significant correlation was found between Per1 and Per2 (P < 0.001) in 130 cases of NSCLC. Similarly, a significant correlation was found between Per2 and Per3 (P=0.045). Patients with lower expression of Per1, Per2 and Per3 had a shorter survival time than those with higher expression. These results indicate that loss of Per may promote tumor progression in NSCLC, and may serve as a novel prognostic biomarker of NSCLC.     

PTEN and Ki67 expression is associated with clinicopathologic features of non-small cell lung cancer

Phosphatase and tensin homolog deleted on chromosome 10（PTEN） and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer（NSCLC）remains unknown.Here,we investigated the expression of PTEN and Ki67 in NSCLC tissues and paired normal lung tissues to identify whether these proteins are associated with lung cancer development and survival.Immunohistochemistry for PTEN and Ki67 was performed on 67 lung cancer tissues and 41 paired adjacent normal lung tissues to detect the expression of these two proteins.The expression of PTEN in NSCLC tissues（32.8%） was significantly lower than that in normal tissues（82.9%,P 〈 0.05）.In contrast,the expression of Ki67 in NSCLC tissues（76.1%） was significantly higher than that in normal tissues（27.3%,P 〈 0.05）.Expression of both PTEN and Ki67 were strongly associated with tumor histology,clinical stage,lymph node metastasis,differentiation and4-year postoperative survival rate（P 〈 0.05）.However,PTEN expression was negatively correlated with Ki67 expression（r =-0.279,P 〈 0.05）.In conclusion,low PTEN expression and Ki67 overexpression are associated with malignant invasion and lymph node metastasis of NSCLC.These proteins may serve as diagnostic and prognostic biomarkers of NSCLC.     

Tumor-stroma ratio is an independent predictor for survival in NSCLC

Tumor-stroma ratio (TSR) has been identified as a new and practicable prognostic factor in some solid tumors. The aim of the study is to evaluate the prognostic value of TSR in non-small cell lung cancer (NSCLC). A total of 404 patients who underwent surgery resection for NSCLC were included in this study. TSR was assessed visually on the hematoxylin-stained tissue sections of surgical specimens. Patients with more than 50% intratumor stroma were quantified as the stroma-rich group and those with less than 50% as the stroma-poor group. In 404 cases of tissue samples, 302 cases were included in the stroma-poor group, while 102 cases in stroma-rich group. The different expression of TSR in NSCLC tissue was not correlated with gender, age, smoking history, tumor diameter, histology, differentiation grade and pTNM staging. In the Cox univariate and multivariate analyses of the 5-year OS, the HRs of the TSR were 1.818 (95% CI; 1.323-2.497; P<0.001) and 1.748 (95% CI; 1.262-2.422; P<0.05), respectively. As for DFS, the HRs were 1.715 (95% CI; 1.249-2.354; P<0.001) and 1.570 (95% CI; 1.135-2.172; P<0.05). Stroma-rich tumors were associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic histological characteristic in NSCLC.     

MicroRNA-153 expression and prognosis in non-small cell lung cancer

Background: miR-153 has been found to be significantly decreased in non-small cell lung cancer (NSCLC) tissues; however, its clinical significance has not been investigated. Methods: The expression patterns of miR-153 in 137 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed using qRT-PCR. The relationships between miR-153 expression and clinicopathological parameters were examined by chi-square test. Kaplan-Meier method and the log-rank test were used to determine the difference in overall survival (OS) rates between two groups. Results: The expression of miR-153 was reduced significantly, compared with adjacent normal lung tissues (P<0.05). We observed that the expression level of miR-153 was positively correlated with the clinical stage (P=0.005), lymph node status (P=0.014), distant metastasis (P=0.004), and differentiated degree (P<0.001) in NSCLC patients. According to the Kaplan-Meier survival analysis, the patients with low miR-153 expression exhibited evidently poorer overall survival rates than those with high miR-153 expression (P=0.003). Multivariate analysis showed that the expression of miR-153 was an independent and significant factor associated with poor OS rates (P=0.002). Conclusion: Decreased expression of miR-153 might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.     

Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan

The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n = 28) were more resistant to reinfection (Fisher's exact test, P < 0.05) than newly recruited canal cleaners (n = 17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (χ² = 19.1, P < 0.0001), significantly larger portal vein diameter (P < 0.05) and enlarged spleen (χ² = 4.2, P < 0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P < 0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P < 0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P < 0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P < 0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P < 0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed.     

Detection and significance of TregFoxP3+ and Th17 cells in peripheral blood of non-small cell lung cancer patients

Introduction

The aim of this study was to explore the relationships between TregFoxP3⁺ cells and Th17 cells and occurrence of lung cancer.

Material and methods

The proportions of TregFoxP3⁺ and Th17 cells, the expression of FoxP3 and RORγt mRNA, and the levels of related cell factors such as transforming growth factor-β (TGF-β), interleukin IL-17 (IL-17) and IL-23 were determined respectively by flow cytometry analysis, real-time-polymerase chain reaction (PCR), and ELISA in peripheral blood of 18 healthy people and 26 patients with non-small cell lung cancer (NSCLC).

Results

The levels of TregFoxP3⁺ and Th17, expression of FoxP3 and RORγt mRNA, and ratios of TregFoxP3⁺/Th17 and FoxP3/RORγt in peripheral blood with NSCLC were higher than those in healthy controls (p < 0.05). The proportion of Th17 cells from NSCLC patients was positively correlated with that of TregFoxP3⁺ (r = 0.81, p < 0.05). The receiver-operating characteristic (ROC) curve demonstrates that the increased level of TregFoxP3⁺/Th17 in the peripheral blood may be a useful indicator in early diagnosis of non-small cell lung carcinoma. The TregFoxP3⁺/Th17 and FoxP3/RORγt levels for patients in stage IV were higher than those of patients in stages I, II, and III (p < 0.05). The levels of TGF-β, IL-17, and IL-23 were higher in NSCLC patients than those in healthy controls.

Conclusions

The results suggest that ratios of Treg/Th17 correlate with the stage of NSCLC.     

Effect of rapamycin (RAPA) on the growth of lung cancer and its mechanism in mice with A549

Objective: To investigate the effects of rapamycin (RAPA) on the tumor growth of lung cancer in the mice bearing A549 and the mechanisms. Methods: 60 mice with A549 lung cancer models established were randomly divided into model group, low RAPA dose group and high RAPA dose group. The low dose group underwent intraperitoneal injection of 1.5 mg/kg RAPA, while the high dose group underwent intraperitoneal injection of 4.5 mg/kg RAPA, and the control group was given the same volume of PBS. 21 d after the administration, the changes of the tumor growth and survival rates of three groups were observed. RT-PCR and Western blot were utilized to analyze Caspase-3 mRNA and protein levels in the tumor tissues of the mice, and TUNEL staining method was used to analyze the cellular apoptosis of tumor tissues. Results: Compared with the model group, the low and high dose groups significantly inhibit tumor growth and have remarkably higher survival rates (P<0.05). The high dose group has obviously better effects on inhibiting tumors and a higher survival rate than low dose group (P<0.05). Compared with the model group, the low and high dose groups have significantly increased Caspase-3 mRNA and protein levels in tumor tissues (P<0.05), and higher cellular apoptosis rates in tumor tissues (P<0.05); Caspase-3 mRNA and protein levels and apoptosis rates of the mice’s tumor tissues of high dose group are markedly higher than those of low dose group (P<0.05). Conclusions: RAPA can significantly increase the expression of Caspase-3 in tumor tissues and promote the apoptosis of tumor tissue cells, and thus achieve good anti-tumor effects.     

High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival

Melanoma associated antigen-A (MAGE-A) is an oncogene and correlated with tumor initiation and development. However the roles of MAGE-A9 in non-small cell lung cancer (NSCLC) are still unknown. We investigated MAGE-A9 mRNA expression in 18 tumor tissues of NSCLC by qRT-PCR and MAGE-A9 protein expression in 213 NSCLC samples of tissue arrays by immunohistochemical staining. We assessed the relationship between MAGE-A9 expression and clinical parameters. The results showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were commonly present in squamous cell carcinomas (P = 0.030). It was also related to larger tumor diameter, lymph node metastasis and later stage grouping with TNM classification (all P < 0.05). Whereas the expression of MAGE-A9 in stromal cells was higher in squamous cell carcinomas as well. Cox regression univariate and multivariable analysis revealed that MAGE-A9 expression in tumor cells of NSCLC (P < 0.001) is an independent prognostic factor in five-year overall survival rate. We concluded that the molecular assessment of MAGEA9 could be considered to improve prognostic evaluation and to identify eligible patients for potential target therapy.     

miR-126 regulated breast cancer cell invasion by targeting ADAM9

Accumulating evidence has shown that microRNAs (miRNAs) deregulation is commonly observed in human malignancies and crucial to cancer metastasis. Herein, we demonstrated that miR-126 play a suppressor role in human breast cancer cells invasion through the direct repression of a disintegrin and metalloprotease 9 (ADAM9). MiR-126 expression was investigated in forty cases of breast cancer specimens by real-time PCR. Transwell assay was conducted to explore the effects of miR-126 on the invasion of human breast cancer cell lines. The impact of miR-126 overexpression on putative target ADAM9 was subsequently confirmed by Western blot analysis. Our results indicated that miR-126 expression was frequently down-regulated in breast cancer specimens compared with adjacent normal tissues (P<0.05). Overexpression of miR-126 significantly reduced (P<0.05) the protein levels of ADAM9, further suppressed (P<0.05) breast cancer cell invasion in vitro. Meanwhile, knockdown of ADAM9 by small interfering RNA (siRNA) also inhibited (P<0.05) breast cancer cell invasion. Thus, our study revealed that miR-126 may act as a tumor suppressor via inhibition of cell invasion by downregulating ADAM9 in breast cancer development.