Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor. However, the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown. The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line.</p><p><b>METHODS</b>Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549). The invasion, proliferation, and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo. The related mechanism was further investigated.</p><p><b>RESULTS</b>Interestingly, OPN knockdown significantly suppressed the invasiveness of A549 cells, but had only a minor effect on the cellular migration and proliferation. Moreover, we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA), and led to an obvious inhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P < 0.001).</p><p><b>CONCLUSIONS</b>Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion, independent of cellular migration and proliferation. OPN could be a new treatment target of NSCLC.</p>

Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor prognosis in stage N2 non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with single station mediastinal lymph node (N2) non-small cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2. The molecular factors which are involved in disease progression remain largely unknown. The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.</p><p><b>METHODS</b>Gene expression analysis was performed using Agilent 4×44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.</p><p><b>RESULTS</b>We identified a 14 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between single station and multilevel N2 NSCLC. Four genes (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients. Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.</p><p><b>CONCLUSIONS</b>Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC. Further, CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.</p>

Epithelial growth factor receptor mutation status to the effective of survival in non-small cell lung cancer after surgery / 中华外科杂志

<p><b>OBJECTIVES</b>To investigate the relationship between the epithelial growth factor receptor (EGFR) mutation status and clinicopathological factors, and to analyze the mutation on the effect in non-small cell lung cancer (NSCLC) after surgery.</p><p><b>METHODS</b>The NSCLC patients who were resected and detected EGFR gene from March 2009 to March 2011 were retrospectively reviewed. The relationship between EGFR mutation status and clinicopathological factors, tumor markers, prognostic was analyzed.</p><p><b>RESULTS</b>The mutation and the wild group had 169 and 214 patients respectively. EGFR mutation in female, non-smoking, adenocarcinoma and less than 60 years old accounted for 63.91%, 61.54%, 88.76% and 62.13% with statistical significance compared with male (χ(2) = 53.490, P = 0.000), smoking (χ(2) = 48.568, P = 0.000), non-adenocarcinoma (χ(2) = 105.560, P = 0.000) and more than 60 years old (χ(2) = 6.057, P = 0.017). Disease free survival (DFS) of the wild group was better than mutation group (χ(2) = 11.329, P = 0.001). In addition, there were some relations between mutation status and excision repair cross complementing (ERCC1) protein, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) and Cyfra21-1. ERCC1(+) (χ(2) = 6.739, P = 0.012), SCC(χ(2) = 16.839, P = 0.000) and Cyfra21-1(χ(2) = 6.638, P = 0.013) more than normal value was common in wild group. Increased CEA was common in mutation group (χ(2) = 5.436, P = 0.023).</p><p><b>CONCLUSIONS</b>EGFR mutation is commonly found in female, non-smoking, adenocarcinoma and less than 60 years old NSCLC patients. The wild group obtains better DFS than mutation group. Tumor markers may predict the mutation status, which need further research.</p>

Treatment and prognostic analysis of 1638 patients with non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study the prognosis and prognostic factors of non-small-cell lung carcinoma (NSCLC) according the new TNM stage system.</p><p><b>METHODS</b>Clinic data of 1638 inpatient cases admitted from January 2001 to January 2005 were retrospectively reviewed. There were 1083 male and 555 female patients in the study and the average age was 59.5 years. All the patients received surgical procedures.</p><p><b>RESULTS</b>The overall 1, 3, 5-year survival rate was 80.0%, 52.3%, 39.0%. The main prognostic factors were bronchial stump, operation type, T stage, N stage, the number of lymph nodes (LNs) in lymph nodes dissection (1 - 10, 11 - 20, and > 20), overall N stations (< 4 and ≥ 4) and postoperative radiotherapy (all P < 0.05). Cox regression suggested that T stage (P = 0.000), N stage (P = 0.000), operation type (P = 0.001) and LNs (P = 0.013) were independent factors affecting the prognosis.</p><p><b>CONCLUSIONS</b>The overall survival rate of NSCLC is poor. T stage, N stage, operation type and LNs are independent factors affecting the prognosis.</p>

Clinical and prognostic analysis of skip N2 metastases in stage IIIA-N2 non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic factors and the distribution pattern of N2 lymph nodes, to analyze the relationship between the survival rate and skip metastasis of non-small cell lung cancer (NSCLC) patients.</p><p><b>METHODS</b>The clinical data of 478 patients with a pN2 stage who underwent resection for non-small cell lung cancer from January 2000 to December 2004 was retrospectively analyzed. Skip group and non-skip group were defined. Characteristics of tumors, ganglionar involvement and survival were analyzed in both groups.</p><p><b>RESULTS</b>The incidence rate of skip N2 metastasis in stage IIIA-N2 NSCLC patients was 40.6%, which was correlated to sex, smoking and the type of histology (P < 0.05). Squamous carcinoma was the main type of skip group (chi² = 7.602, P = 0.022). The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe (57%) compared to the lower lobe (43%) (chi² = 5.097, P = 0.024). Superior nodes were more frequently involved by skip group (chi² = 7.046, P = 0.030). Moreover, the relationship between the primary tumor location and N2 positive lymph nodes were described as follows: right upper lobe cancer displayed skip-N2 nodal metastasis mostly in the 2nd, 3rd and 4th station, right middle and lower lobe mostly in the 7th station, left upper lobe mostly in the 5th and 6th station (71.7%), and left lower lobe mostly in the 7th and 9th station. The 5-year survival rate of pN2 patients with skip metastasis was 22.1% compared to 13.6% in patients with involvement of N1 and N2 nodes (P = 0.001). Survival analysis showed that skip N2 metastasis was an independent risk factor of stage IIIA NSCLC.</p><p><b>CONCLUSIONS</b>The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe and in the superior nodes. Skip metastasis is an independent prognostic factor of survival. The presence of skip metastasis seems to be a unique subgroup of pN2 disease in NSCLC.</p>

A clinical and prognostic retrospective analysis of IIIA-N2 non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVES</b>To analyze the clinical conditions of postoperative patients with IIIA-N2 non-small cell lung cancer (NSCLC) and the prognostic factors related with survival of NSCLC, and to investigate the influence of operation and therapy on prognosis.</p><p><b>METHODS</b>Clinical data of 657 inpatient cases with IIIA-N2 NSCLC admitted from January 2000 to December 2005 was retrospectively reviewed. The Kaplan-Meier method was used for survival analysis. The Log-rank law was applied to analyze the relationship between the variables and the prognosis in monovariate analysis, while Cox proportional hazard regression model was used to make multivariate analysis.</p><p><b>RESULTS</b>The 1-, 3-and 5-year accumulative survival rates of the operative patience were 64.4%, 26.0% and 17.9%, respectively. The median survival time was 18 months. In monovariate analysis, the main unfavorable factors that affect life span involve were the diameter of tumor, T stage, skip metastasis of N2 lymph node, the number of metastatic lymph nodes, the metastasis of subcarinal lymph nodes, adjuvant chemotherapy, the cycle of adjuvant chemotherapy, postoperative radiotherapy, and the modality of therapy (the effect of naive surgery was disappointed, while the prognosis of the patients with adjuvant chemoradiotherapy was better than those with chemotherapy alone). A multivariate analysis using Cox regression identified 5 factors of prognosis: the diameter of tumor (P = 0.001), the metastasis of subcarinal lymph nodes (P = 0.019), the number of metastatic lymph nodes (P = 0.006), the cycle of adjuvant chemotherapy (P = 0.007), postoperative radiotherapy (P = 0.055), and adjuvant chemoradiotherapy (P = 0.026).</p><p><b>CONCLUSIONS</b>The 5-year survival rate of the patients with IIIA-N2 Non-small cell lung cancer is poor. Tumor size, the metastasis of subcarinal lymph nodes, the number of metastatic LNs, the cycle of adjuvant chemotherapy, and postoperative radiotherapy have an effect on the prognosis. The prognosis of postoperative patients with single-level N2 and multi-level N2 disease is similar, and the key point of survival is the number of nodes involved. The therapeutic effect of patience given adjuvant chemoradiotherapy is superior to those treated with adjuvant chemotherapy.</p>

The function of the level of serum carcinoembryonic antigen on early recurrence of non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To explore clinical and pathological factors correlating with early recurrence of resected non small cell lung cancer (NSCLC), and to further understand the function of serum carcinoembryonic antigen (CEA) on NSCLC.</p><p><b>METHODS</b>93 patients of NSCLC were selected. All of them received resection and were followed up for more than one year. The first time of recurrence was recorded. Logistic univariate and multivariable analysis were used to find the factors that affect the early recurrence of NSLSC, including age, sex, serum CEA level, tumor size, tumor location, tumor differentiation, histological type and clinical staging, and the ability of factors predicting the recurrence were compared by receiver operating characteristic (ROC) curve.</p><p><b>RESULTS</b>Of all the clinical and pathological factors that are correlated with early recurrence of NSCLC, the serum carcinoembryonic antigen (CEA) value, clinical staging, and tumor difference are of statistical significance. The preoperative serum CEA value is the most valuable factor to predict early recurrence of NSCLC (ROC area: 0.843, 95% CI: 0.723 approximately 0.963, P = 0.000). When preoperative serum CEA value > 10 micro g/L, patients of NSCLC will have an early recurrence rate of 88%; and when preoperative serum CEA value </= 10 micro g/L, the probability of no early recurrence is 92%.</p><p><b>CONCLUSION</b>For the patients with respectable NSCLC, it is very important to know the precise clinical stage and pathological difference, and so is the preoperative serum CEA value. When preoperative serum CEA value > 10 micro g/L, even if the lesion is of early stage and well differenced, the general situation of patients should be carefully examined for the prompt and accurate treatment to them and close follow up is needed to treat these patients.</p>

The effect of nuclear transcription factor-kappaB decoy oligodeoxynucleotides on the intimal hyperplasia in vein graft / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of nuclear transcription factor-kappaB decoy oligodeoxynucleotides (NFkappaB decoyODNs) on the intimal hyperplasia (IH) in vein graft in rats.</p><p><b>METHODS</b>Autogenous vein graft model for 72 Wistar rats was established, and the interior jugular vein was transplanted to common jugular artery by microsurgical technique. The rats were divided into 6 groups according to different processing methods, including NFkappaB decoyODNs 50 microg and 200 microg, scramble decoyODNs 50 microg and 200 microg, control and lipofectin + pluronic teams. Vein graft samples were harvested in 1 or 2 weeks after surgery and ICAM-1 mRNA were measured by RT-PCR. Western blotting and immunohistochemistry methods were also employed to detect the expression of p65 and ICAM-1. IH was compared at the same time.</p><p><b>RESULTS</b>The intimal hyperplasia was evident in 1 or 2 weeks after vein graft, and ameliorated by 50 microg of NFkappaB decoyODNs with inhibition rate from 22% to 31%, 200 microg of NFkappaB decoyODNs had a higher inhibition rate from 41% to 53%. However, no effect was found in the other teams. The expression of ICAM-1 mRNA was also inhibited significantly by NFkappaB decoyODNs and more obvious in 2 weeks after surgery. Expression of ICAM-1 and p65 decreased greatly in NFkappaB decoyODNs team, which has a inhibition rate from 30% to 57%.</p><p><b>CONCLUSION</b>Transfection of NFkappaB decoyODNs can inhibit the IH after vein graft, which may be accomplished by the inhibition of gene expression of ICAM-1.</p>