1.Macrophage Inhibitory Cytokine-1 as a Novel Diagnostic and Prognostic Biomarker in Stage I and II Nonsmall Cell Lung Cancer.
Yu-Ning LIU ; Xiao-Bing WANG ; Teng WANG ; Chao ZHANG ; Kun-Peng ZHANG ; Xiu-Yi ZHI ; Wei ZHANG ; Ke-Lin SUN
Chinese Medical Journal 2016;129(17):2026-2032
BACKGROUNDIncreased level of serum macrophage inhibitory cytokine-1 (MIC-1), a member of transforming growth factor-μ superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whether serum level of MIC-1 can be a candidate diagnostic and prognostic indicator for early-stage nonsmall cell lung cancer (NSCLC).
METHODSA prospective study enrolled 152 patients with Stage I-II NSCLC, who were followed up after surgical resection. Forty-eight patients with benign pulmonary disease (BPD) and 105 healthy controls were also included in the study. Serum MIC-1 levels were measured using an enzyme-linked immunosorbent assay, and the association with clinical and prognostic features was analyzed.
RESULTSIn patients with NSCLC, serum protein levels of MIC-1 were significantly increased compared with healthy controls and BPD patients (all P< 0.001). A threshold of 1000 pg/ml of MIC-1 was found in patients with early-stage (Stage I and II) NSCLC, with sensitivity and specificity of 70.4% and 99.0%, respectively. The serum levels of MIC-1 were associated with age (P = 0.001), gender (P = 0.030), and T stage (P = 0.022). Serum MIC-1 threshold of 1465 pg/ml was found in patients with poor early outcome, with sensitivity and specificity of 72.2% and 66.1%, respectively. The overall 3-year survival rate of NSCLC patients with high serum levels of MIC-1 (≥1465 pg/ml) was lower than that of NSCLC patients with low serum MIC-1 levels (77.6% vs. 94.8%). Multivariate Cox regression survival analysis showed that a high serum level of MIC-1 was an independent risk factor for reduced overall survival (hazard ratio = 3.37, 95% confidential interval: 1.09-10.42, P= 0.035).
CONCLUSIONThe present study suggested that serum MIC-1 may be a potential diagnostic and prognostic biomarker for patients with early-stage NSCLC.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; mortality ; pathology ; surgery ; Enzyme-Linked Immunosorbent Assay ; Female ; Growth Differentiation Factor 15 ; blood ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Survival Rate
2.Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer.
Kyung Hee KIM ; Tae Yun PARK ; Ji Yeun LEE ; Sang Min LEE ; Jae Joon YIM ; Chul Gyu YOO ; Young Whan KIM ; Sung Koo HAN ; Seok Chul YANG
Journal of Korean Medical Science 2014;29(4):507-511
Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 x 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.
Aged
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Blood Platelets/*cytology
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Carcinoma, Non-Small-Cell Lung/*diagnosis/mortality/pathology
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Female
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Fibrinogen/*analysis
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Humans
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Lung Neoplasms/*diagnosis/mortality/pathology
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Male
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Middle Aged
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Neoplasm Staging
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Platelet Count
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Prognosis
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Retrospective Studies
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Survival Rate
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Thrombocytosis/complications/diagnosis
3.Elevated Serum C-Reactive Protein as a Prognostic Marker in Small Cell Lung Cancer.
Soojung HONG ; Young Ae KANG ; Byoung Chul CHO ; Dae Joon KIM
Yonsei Medical Journal 2012;53(1):111-117
PURPOSE: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). MATERIALS AND METHODS: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. RESULTS: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). CONCLUSION: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.
Aged
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Aged, 80 and over
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Biological Markers/blood
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C-Reactive Protein/*metabolism
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Female
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Humans
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Kaplan-Meier Estimate
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Lung Neoplasms/*blood/*mortality
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Male
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Middle Aged
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Predictive Value of Tests
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Prognosis
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Small Cell Lung Carcinoma/*blood/*mortality
5.Vascular endothelial growth factor C as a predictor of early recurrence and poor prognosis of resected stage I non-small cell lung cancer.
Shuo Chueh CHEN ; Chuen Ming SHIH ; Guan Chin TSENG ; Wei Erh CHENG ; Jean CHIOU ; Michael HSIAO ; Min Liang KUO ; Jen Liang SU ; Chih Yi CHEN
Annals of the Academy of Medicine, Singapore 2011;40(7):319-324
INTRODUCTIONStage I non-small cell lung cancer (NSCLC) is potentially curable after completely resection, but early recurrence may infl uence prognosis. This study hypothesises that vascular endothelial growth factor C (VEGF-C) plays a key role in predicting early recurrence and poor survival of patients with stage I NSCLC.
MATERIALS AND METHODSThe expression of VEGF-C was immuno-histochemically (IHC) analysed in tumour samples of primary stage I NSCLC and correlated to early recurrence (< 36 months), disease-free survival, and overall survival in all 49 patients.
RESULTSEarly recurrence was identifi ed in 16 patients (33%), and the early recurrence rate in strong and weak VEGF-C activity was significantly different (P = 0.016). VEGF-C was also an independent risk factor in predicting early recurrence (HR = 3.98, P = 0.02). Patients with strong VEGF-C staining also had poor 3-year disease-free survival (P = 0.008) and overall survival (P = 0.007).
CONCLUSIONStrong VEGF-C IHC staining could be a biomarker for predicting early recurrence and poor prognosis of resected stage I NSCLC, if the results of the present study are confirmed in a larger study. A more aggressive adjuvant therapy should be used in this group of patients.
Adult ; Aged ; Aged, 80 and over ; Biomarkers ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; mortality ; pathology ; surgery ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Taiwan ; Vascular Endothelial Growth Factor A ; blood ; metabolism
6.Analysis of 41 cases of primary hypervascular non-small cell lung cancer treated with embolization of emulsion of chemotherapeutics and iodized oil.
Lingfei LUO ; Hongwu WANG ; Hongming MA ; Hang ZOU ; Dongmei LI ; Yunzhi ZHOU
Chinese Journal of Lung Cancer 2010;13(5):540-543
BACKGROUND AND OBJECTIVETranscatheter arterial chemotherapy and embolization is the main method in the treatment of lung cancer, but most of the reports do not study individually to small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), hypovascular and hypervascular lung cancer. The pre-embolization perfusion of hemotherapeutics is still being used routinely and seldom report to iodized oil embolization. The article summarized the quality of life after the treatment, clinical efficiency, survival time and complications to evaluate the clinical effect of primary hypervascular NSCLC treated with embolization of emulsion of chemotherapeutics and iodized oil.
METHODSThe study totally analyzed 41 cases which confirmed by pathology and follow up study from January, 2008 to January 2009. The CT scan with IV contrast demonstrates over moderate enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15 cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases. Superselective incubation with microcatheter under DSA, to embolize the capillary bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the supply artery of the tumor with gelatin foam microparticle. The liquefied iodized oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and to compare with the references of 2007-2009.
RESULTSThe KPS is widely acclaimed after the treatment (P < 0.05), no complete response (CR), 31 cases of partial response (PR), 7 cases of no change (NC) and 3 cases of progressive disease (PD), the total efficiency (CR+PR) is 75.6%. The clinical efficiency (CR+PR+NC) is 92.68%. 33 cases of total survival tome over 12 months (80.48%), IIIb stage 29/34 (85.29%), IV stage 4/7 (57.14%). 1 case with severe complication-spinal injury.
CONCLUSIONTo treat primary hypervascular NSCLC with simple embolization of emulsion of chemotherapeutics and iodized oil is very useful and can avoid the side effect of chemotherapeutics. The key point to avoid spinal injury and other severe complications is to distinguish the spinal aretery and intratumor AV fistula by using superselective incubation with microcatheter under DSA.
Carcinoma, Non-Small-Cell Lung ; blood supply ; mortality ; therapy ; Chemoembolization, Therapeutic ; Emulsions ; Female ; Humans ; Iodized Oil ; administration & dosage ; Lung Neoplasms ; blood supply ; mortality ; therapy ; Male ; Middle Aged
7.Activated changes of platelet ultra microstructure and plasma granule membrane protein 140 in patients with non-small cell lung cancer.
Yi ZHUGE ; Jian-ying ZHOU ; Guang-die YANG ; De-ling ZU ; Xiao-liang XU ; Ming-qing TIAN ; Guo-hua LU
Chinese Medical Journal 2009;122(9):1026-1031
BACKGROUNDNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.
METHODSOne hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.
RESULTSTransmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of a-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2 +/- 2.7) microg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8 +/- 12.3) microg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of a-granules (r = 0.514, P < 0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r = 0.84, P < 0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose a-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, chi(2) = 17.38, P < 0.01).
CONCLUSIONSThere are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets may play an important role in the generation and growth of lung cancer. These changes can be used as a diagnostic index of severity, progression, and prognosis of NSCLC.
Adult ; Aged ; Blood Platelets ; ultrastructure ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; mortality ; ultrastructure ; Female ; Humans ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; P-Selectin ; blood ; Survival Analysis
8.18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer.
Zhen-jiang ZHANG ; Jing-han CHEN ; Long MENG ; Jia-jun DU ; Lin ZHANG ; Ying LIU ; Hong-hai DAI
Chinese Medical Journal 2007;120(2):125-131
BACKGROUNDThe outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of (18)F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC.
METHODSA retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUV(max)), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUV(max) and other factors was also analyzed.
RESULTSPatients with SUV(max) more than 11 had a disease-free survival and overall survival shorter than patients with SUV(max) less than 11 in univariate analyses (P < 0.001, P = 0.002). In the multivariate analysis, SUV(max) (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUV(max) (dichotomized by 11) were independent predictors for the overall survival. Associations of SUV(max) with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group.
CONCLUSIONS(18)F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood supply ; diagnostic imaging ; mortality ; pathology ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lung Neoplasms ; blood supply ; diagnostic imaging ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Radionuclide Imaging
9.The Relationship between the Serum Intercellular Adhesion Molecule-1 Level and the Prognosis of the Disease in Lung Cancer.
Hun Sub SHIN ; Chan Hee JUNG ; Hyun Duk PARK ; Seung Sei LEE
The Korean Journal of Internal Medicine 2004;19(1):48-52
BACKGROUND: Adhesion molecules are related to cell-to-cell interaction and inflammatory interaction. In addition, adhesive interactions between tumor cells and adjacent cells and/or extracellular matrix play important roles in the complex process of tumor growth and development. Among these adhesion molecules, expression of intercellular adhesion molecule-1 (ICAM-1) has been identified in colon cancer, bladder cancer, lung cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. In the current study, we analyzed serum ICAM-1 concentrations to investigate the relationship between the serum ICAM-1 level and prognosis in patients with lung cancer METHODS: Serum ICAM-1 was measured in 84 patients with lung cancer according to the pathologic type and clinical stage using the ICAM-1 ELISA kit. The Kaplan-Meier method was used to analyse survival time. RESULTS: There was no difference in serum ICAM-1 concentration among the different stages of lung cancer. Furthermore, there was no difference observed between histologic tumor type with regard to serum ICAM-1 concentration. Although the difference was not significant, the overall survival times of patients with a low serum ICAM-1 concentration (< 306 ng/mL) was longer than that of patients with a high concentration (> or=306 ng/mL) in non-small cell lung cancer patients. CONCLUSION: These results suggest that high levels of serum ICAM-1 reflect poor prognosis for patients with non-small cell lung cancer.
Aged
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Carcinoma, Non-Small-Cell Lung/*blood/mortality/pathology
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Carcinoma, Small Cell/*blood/mortality/pathology
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Female
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Human
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Intercellular Adhesion Molecule-1/*blood
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Lung Neoplasms/*blood/mortality/pathology
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Male
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Middle Aged
;
Neoplasm Staging
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Prognosis
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Survival Analysis
10.Prognostic factors in patients with small cell lung cancer.
Li-hua SONG ; Xian-rang SONG ; Xi-qin ZHANG ; Jie-lin QI ; Xiu-ju LI ; He TIAN ; Bing BU
Chinese Journal of Oncology 2004;26(7):413-416
OBJECTIVETo investigate the prognostic factors of small cell lung cancer (SCLC) and establish a reliable model of clinical prognostic index.
METHODSKaplan-Meier and Cox regression were used to analyze the relationship between survival time and prognostic factors in 60 cases of SCLC. The prognostic factors included clinical and laboratory parameters, serum cytokeratin fragment 19 (CYFRA21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R).
RESULTSKaplan-Meier analysis showed that poor prognosis was in patients with KPS < 80 or extensive disease and unrelated to other clinical parameters such as age, sex and smoking index, and in patients with serum NSE > 30 micro g/L, CEA > 5.0 micro g/L, CA125 > 37 KU/L and sIL-2R > 500 KU/L. Serum IL-2 and CYFRA21-1 were also elevated, but had no significant prognostic value. Multivariate analysis indicated that serum NSE, stage and treatment of disease were independent prognostic factors. The three prognostic factors enabled establishment of a prognostic index (PI) based on a simple algorithm: PI = NSE (0 if < or = 30 micro g/L, 1 if > 30 microg/L) + stage (0 = LD, 1 = ED) + CEA (0 if < or = 5.0 microg/L, 1 if > 5.0 microg/L).
CONCLUSIONThe stage of disease, systemic treatment and the level of serum NSE are independent prognostic factors. Without considering the influence of treatment-related factors on survival, the levels of serum CEA, NSE and stage of disease before treatment are significant independent prognostic factors. PI calculated on the basis of CEA, NSE and stage is recommended to predict the survival of SCLC.
Adult ; Aged ; Biomarkers, Tumor ; blood ; Brain Neoplasms ; secondary ; Carcinoma, Small Cell ; mortality ; secondary ; therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; mortality ; pathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Survival Rate

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