Value of Combined Detection of Cytokines and Tumor Markers in the Differential Diagnosis of Benign and Malignant Solitary Pulmonary Nodules / 中国肺癌杂志

BACKGROUND@#Solitary pulmonary nodule has received increasing attention in recent years. A couple of lung nodules have been recognized as primary malignant tumors, which leads to an urgent need in enhancing the diagnosis of benign/malignant lung nodules at clinical settings. This study aims to explore the value of the combined detection of cytokines and tumor markers in differencing benign and malignant solitary pulmonary nodules in diagnose.@*METHODS@#With 81 solitary pulmonary nodules cases with a clear diagnosis, the general clinical data, nodule imaging features, pathological diagnosis data, serological index cytokine series and tumor marker expression levels were collected in groups. Both single factor and multi-factors analysis were conducted to screen out the serum influence indexes that can predict the malignant probability of lung nodules, and mean while binary logistic regression analysis was used to construct joint indexes; After receiver operating characteristic curve (ROC) was drawn, the area under the curve and the corresponding sensitivity, specificity and positive of each index predicted value, negative predicted value and accuracy could be calculated with a view to determine the statistical significance of area under the curve (AUC).@*RESULTS@#There are differences in the distribution of malignant solitary pulmonary nodules at different locations, with the highest proportion of the right upper lobe (40.4%). The serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), interleukin-6 (IL-6), interleukin-8 (IL-8) in the malignant nodule group were higher than those in the benign nodule group. Logistic regression analysis suggests that CEA, IL-6 and IL-8 are independent risk factors for predicting malignant nodules. ROC curve analysis shows that the areas under the curve of the individual indicators CEA, IL-6 and IL-8 are 0.642, 0.684 and 0.749. The comparison result of the test efficiency of the area under the curve suggests that CEA+IL-6+IL-8 has a larger area under the curve and higher detection efficiency.@*CONCLUSIONS@#CEA, IL-6 and IL-8 are independent risk factors for malignant solitary pulmonary nodules. The combined detection of cytokines and tumor markers has played a role in the differential diagnosis of benign and malignant lung nodules. The diagnostic value of the combined detection of CEA+IL-6+IL-8 is the highest.

Stathmin overexpression is associated with growth, invasion and metastasis of lung adenocarcinoma.

Stathmin has been investigated as a tumor biomarker because it appear to be associated with tumorigenesis; however, the effect of stathmin in lung adenocarcinoma (LAC) remains poorly understood. The purpose of this study was to examine the expression of stathmin in lung adenocarcinoma, and to disclose the relationship between them. The expression of stathmin was examined by RT-PCR, IHC and Western blot. Furthermore, small interfering RNA (shRNA)-mediated silencing of stathmin was employed in LAC cells to investigate cell proliferation, invasion and apoptosis. In this study, we showed that overexpression of stathmin was significantly associated with poorly differentiated, lymph node metastasis and advance TNM stages of lung adenocarcinoma. And silencing of stathmin expression inhibited the proliferation, migration and invasion of lung adenocarcinoma PC-9 cells, and retarded the growth of PC-9 cells xenografts in nude mice. Additionally, the anticarcinogenic efficacy of stathmin silencing might be involved in P38 and MMP2 signaling pathways. In conclusion, these results showed that stathmin expression was significantly up-regulated in LAC, which may act as a biomarker for LAC. Furthermore, silence of stathmin inhibiting LAC cell growth indicated that stathmin may be a promising molecular target for LAC therapy.

The role and potential mechanisms of LncRNA-TATDN1 on metastasis and invasion of non-small cell lung cancer.

The invasion and metastasis of malignant tumor cells lead to normal tissue destruction and are major prognostic factors for many malignant cancers. Long non-coding RNA (LncRNA) is associated with occurrence, development and prognoses of non-small cell lung cancer (NSCLC), but its mechanisms of action involved in tumor invasion and metastasis are not clear. In this study, we screened and detected the expression of LncRNA in two NSCLC lines 95D and 95C by using high throughput LncRNA chip. We found that TATDN1 (Homo sapiens TatD DNase domain containing 1, TATDN1), one of LncRNAs, was highly expressed in 95D cells and NSCLC tumor tissues compared to 95C cells. Knockdown of TATDN1-1 by shRNA significantly inhibited cell proliferation, adhesion, migration and invasion in 95D cells. Further mechanism study showed that TATDN1 knockdown suppressed the expression of E-cadherin, HER2, ß-catenin and Ezrin. Moreover, knockdown TATDN1 also inhibited tumor growth and metastasis in a 95D mouse model in vivo by inhibiting ß-catenin and Ezrin. These data indicate that TATDN1 expression is associated with 95D cells' higher potential of invasion and metastasis, and suggest that TATDN1 may be a potential prognostic factor and therapeutic target for NSCLCs.

Co-overexpression of Hsp90-ß and annexin A1 with a significantly positive correlation contributes to the diagnosis of lung cancer.

AIM: Hsp90-ß and annexin A1 have been demonstrated to be associated with tumorigenesis. However, the effect of Hsp90-ß and annexin A1 in lung cancer remains poorly understood. In this research, the correlation of Hsp90-ß and annexin A1 in lung cancer patients were analyzed. METHODS: The expression levels of Hsp90-ß and annexin A1 were examined by immunohistochemistry and ELISA. RESULTS: Lung cancer tissues and serum exhibited higher co-expression of Hsp90-ß and annexin A1 than control groups (p < 0.05). Hsp90-ß and annexin A1 could discriminate lung cancer from the control groups (sensitivity of Hsp90-ß was 80.2% in tissues and 96% in serum; specificity of Hsp90-ß was 80% in tissues and 83.33% in serum; sensitivity of annexin A1 was 68.76% in tissues and 95.23% in serum; specificity of annexin A1 was 75% in tissues and 85.7% in serum) and multi-index combined detection had a better diagnostic value. CONCLUSION: The expression levels of Hsp90-ß and annexin A1 positively correlated and such co-overexpression of Hsp90-ß and annexin A1 contributed to lung cancer diagnosis.

Maintenance therapy of gefitinib for non-small-cell lung cancer after first-line chemotherapy regardless of epidermal growth factor receptor mutation: a review in Chinese patients.

PURPOSE: Gefitinib is a well known therapy for non-small-cell lung cancer (NSCLC). The purpose of this study was to review clinical reports of gefitinib as maintenance therapy after first-line chemotherapy regardless of epidermal growth factor receptor (EGFR) mutation, and assess its efficacy and safety in Chinese patients. MATERIALS AND METHODS: Systematic computerized searches of the following databases were conducted from the start of each database up to July 2012; these include Medline, EMBASE, CNKI and www.clinicaltrials.gov. Terms searched include 'non-small-cell lung cancer', 'NSCLC', 'lung cancer', 'lung tumor', 'gefitinib', 'Iressa', 'EGFR' and 'epidermal growth factor receptor tyrosine kinase inhibitors'. A total of 22 studies were reviewed. RESULTS: In general, the overall response rate (ORR), disease control rate (DCR) and one year survival (OYS) of gefitinib maintenance therapy were 30.89%, 67.5% and 50.6% respectively, in addition, the median overall survival (OS) and median progression free survival (PFS) were 13.09 and 7.88 months respectively. Moreover, ORR, DCR, median survival time (MST) and PFS of female, nonsmoking, lung adenocarcinoma (LAC) patients and patients with rash had higher performance than male, smoking, non-LAC patients and patients without rash (p < 0.05). The adverse events (AEs) were mainly skin rashes and diarrhea, most of which were grades 1 or 2 and were well tolerated. CONCLUSION: Gefitinib produced encouraging efficacy, safety and survival when delivered as maintenance therapy for NSCLC in Chinese patients after first-line chemotherapy regardless of EGFR mutation, especially for the patients who were female, non-smokers, LAC and with rash. Key limitations of this review include limited subgroup data, small sample sizes, and the lack of EGFR/KRAS data.