Identification of annexin A1 as a proinvasive and prognostic factor for lung adenocarcinoma.
ABSTRACT Metastasis is the most common cause of death in lung cancer patients and is a major obstacle to the successful treatment. To discover novel metastasis-related proteins in lung adenorcinoma (AdC), quantitative proteomic analysis was performed between primary lung AdC tissues with (LNM AdC) and without lymph node metastasis (non-LNM AdC). In this study, annexin A1 was identified to be significantly up-regulated in LNM AdC compared with non-LNM AdC. Immunohistochemistry showed that annexin A1 over-expression was frequently observed in LNM AdCs and matched lymph node metastases compared with non-LNM AdCs. Annexin A1 over-expression was significantly associated with advanced clinical stage (P < 0.05) and lymph node metastasis (P < 0.05) and increased relapse rate (P < 0.05) and decreased overall survival (P < 0.05) in lung AdCs. Cox regression analysis indicated annexin A1 over-expression was an independent prognostic factor. Furthermore, suppression of annexin A1 expression by siRNA interference significantly inhibited the invasion ability of lung adenocarcinoma cell A549 in vitro. In conclusion, annexin A1 expression correlated with tumor stage, lymph node metastasis, relapse, and patient survival. Annexin A1 is proposed to function importantly in the progression of lung AdC.
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ABSTRACT: Pyruvate kinase isoenzyme M2-PK is instrumental to tumour metabolism and hence over-expressed in tumour cells leading to detectable plasma concentrations. To assess the degree of association between M2-PK plasma concentrations and ovarian cancer and to determine the cut-off values for its sensitivity and specificity for differentiating between benign and malignant ovarian disease. The Gynaecological Cancer Centre at both King's College and St. Thomas' Hospitals, London, UK. Patients with suspected ovarian cancer referred to the above centre were recruited prospectively during the years 2004-2005. Blood samples were collected before surgery for plasma M2-PK assays. Results were assessed with respect to cancer diagnosis, patient and tumour characteristics. Statistical analysis including the receiver operator characteristic (ROC) curve was performed using Analyse-It and SPSS V 13. 100 patients with age range 14-88 years and a median of 57 years were recruited in the study. Of whom 52 were diagnosed with invasive ovarian cancer. Of these 35 (67%) were Stage III and above with two secondary tumours. M2-PK was not related to patient age (p = 0.43). There was a significant correlation between CA125 and M2-PK (p < 0.001). The mean M2-PK concentration in cancer patients was 52 U/ml versus 27 U/ml in patients with benign conditions (p < 0.001). At a cut-off value of 22 U/ml the sensitivity of M2-PK for detecting cancer was 70% with a specificity of 65%. M2-PK was significantly raised in ovarian cancer patients, however its role in clinical practice needs further evaluation.European journal of gynaecological oncology 02/2007; 28(2):83-8. · 0.58 Impact Factor
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ABSTRACT: To determine the epidemiology, pathology and patterns of care for patients with non-small cell lung cancer (NSCLC) in the United States. In 2001 the National Cancer Data Base, under direction of the American College of Surgeons, conducted a patient care evaluation study in 719 hospitals. We collected information on patient demographics and histories, diagnostic and staging methods, pathology, and initial treatment. Information on 40,909 patients was obtained; 93% were smokers. Slightly more than half were older than 70 years; 58.5% were male and 35% had adenocarcinoma. Comorbid conditions were present in 71.8% and 22% had a prior malignancy. A chest CT scan was performed in 92% of patients and PET scans in 19.3%. Mediastinoscopy was performed in 20.3%. 67.2% of patients had Stage III or IV disease. More of the Hispanic, Asian or Black patients than White had Stage IV disease (p<0.01). Treatment was multimodality in a little over 30% of patients. Surgery alone was primarily utilized for patients in Stage I or II. Choice of treatment correlated more with stage and age than comorbidities. Our results substantiated the pattern of increasing proportions of women with NSCLC and the increasing frequency of adenocarcinoma. Most patients presented with Stage III or IV disease. Ethnic minorities were more likely to present in late stage disease than Whites. Treatment strategies depended more on stage and age than comorbid burden. Older patients were less likely to receive surgery and more likely to be treated with radiation only or have no treatment.Lung Cancer 09/2007; 57(3):253-60. · 3.39 Impact Factor
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ABSTRACT: The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer.Proceedings of the National Academy of Sciences 09/2001; 98(17):9824-9. · 9.74 Impact Factor