BACKGROUND: Non-small cell lung cancer (NSCLC) have the highest incidence of lung cancer which treatment principles are diagnosis and treatment as early as possible. Because of its insidious onset and lack of specific markers for early screening, most patients are at an advanced stage when diagnosed which results in a low 5-year survival rate and poor prognosis. Therefore Exploring a sensitive biomarker is the focus of current diagnosis and treatment of lung cancer. The aim of this study is to investigate the biological markers in serum of patients with I-IIb stage NSCLC by differential peptidomics analysis. METHODS: The serum peptidome was compared and analyzed among the groups of normal health controls, benign lung diseases and early stage NSCLC patients using a nano ultra-performance liquid chromatography combined with a quadrupole-orbitrap mass spectrometer. The differentially expressed polypeptides were identified and analyzed quantitatively to screen the tumor biomarkers for the early diagnosis of NSCLC patients. RESULTS: According to the Swiss-Prot database, a total of 545 polypeptides originated from 118 proteins were identified. The spectral numbers of serum polypeptides in each group were compared and a total of 201 polypeptides differentially expressed were found. Following a quantitative analysis of the above peptides, we found that there were 7 peptides with the coefficient of variation (CV) less than 30% and among them the peptide of QGAKIPKPEASFSPR from ITIH4 was down-regulated and the peptide of CDDYRLC from MGP was up-regulated in NSCLC group. CONCLUSIONS The tumor biomarkers obtained by serum peptidome technology can provide a new clue for early diagnosis of NSCLC and the specific peptides hydrolyzed from ITIH4 and MGP may be the serum biological markers for early NSCLC patients.
Adult ; Aged ; Amino Acid Sequence ; Biomarkers, Tumor ; blood ; chemistry ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; Early Detection of Cancer ; Female ; Humans ; Lung ; pathology ; Lung Neoplasms ; blood ; diagnosis ; Male ; Middle Aged ; Neoplasm Staging ; Peptides ; blood ; chemistry ; Proteomics ; methods ; Sensitivity and Specificity ; Young Adult

BACKGROUND: Current research shows that platelet to lymphocyte ratio (PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer (NSCLC) through meta-analysis. METHODS: Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet (CNKI), China Biomedical Medicine disc (CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival (OS) and disease-free survival (DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk (HR) and 95% confidence interval (95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. RESULTS: We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I²=46.2%, Pheterogeneity=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.41, 95%CI: 1.14-1.74, P=0.001, I²=46.2%, Pheterogeneity=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group (P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment. CONCLUSIONS Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.
Blood Platelets ; cytology ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; pathology ; Humans ; Lung Neoplasms ; blood ; diagnosis ; pathology ; Lymphocytes ; cytology ; Platelet Count ; Prognosis

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Non-Small-Cell Lung/blood/diagnosis/*drug therapy/genetics ; Cell Line, Tumor ; Cisplatin/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/blood/diagnosis/*drug therapy/genetics ; Male ; Mice ; Mice, Nude ; MicroRNAs/blood/*genetics ; Middle Aged ; Prognosis ; Survival Analysis ; Treatment Outcome

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Non-Small-Cell Lung/blood/diagnosis/*drug therapy/genetics ; Cell Line, Tumor ; Cisplatin/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/blood/diagnosis/*drug therapy/genetics ; Male ; Mice ; Mice, Nude ; MicroRNAs/blood/*genetics ; Middle Aged ; Prognosis ; Survival Analysis ; Treatment Outcome

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 ; Blood Platelets/*cytology ; Carcinoma, Non-Small-Cell Lung/*diagnosis/mortality/pathology ; Female ; Fibrinogen/*analysis ; Humans ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Prognosis ; Retrospective Studies ; Survival Rate ; Thrombocytosis/complications/diagnosis

No abstract available.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Blood Cells/pathology ; Bone Marrow Cells/pathology ; Carcinoma, Non-Small-Cell Lung/*drug therapy/radiotherapy ; Humans ; Karyotyping ; Leukemia, Megakaryoblastic, Acute/*diagnosis/etiology ; Lung Neoplasms/*drug therapy/radiotherapy ; Male

To date, most clinical data on pro-gastrin-releasing peptide (proGRP) have been based on serum concentrations. This study evaluated the agreement between proGRP levels in fresh serum and plasma in patients with various lung diseases. Pairs of serum and EDTA plasma were collected from 49 healthy individuals. At the same time, EDTA plasma of 118 lung cancer patients and 23 patients with benign pulmonary diseases were prospectively collected. Compared to serum, plasma proGRP concentrations were higher by an average of 103.3%. Plasma proGRP was higher in malignancy (336.4 +/- 925.4 pg/mL) than in benign conditions (40.1 +/- 11.5 pg/mL). Small cell lung cancer (SCLC) patients showed higher levels of proGRP (1,256.3 +/- 1,605.6 pg/mL) compared to other types of lung cancer. Based on the ROC curve analyses at a specificity of 95%, the diagnostic sensitivity of plasma proGRP was estimated to be 83.8% in distinguishing SCLC from all the other conditions, and 86.5% for discriminating SCLC from the nonmalignant cases. Among the SCLC cases, limited stage disease had lower levels of plasma proGRP than extensive disease. When measuring circulating levels of proGRP, the use of plasma is preferred over serum. Plasma proGRP has a potential marker for discriminating SCLC from nonmalignant conditions or non-small cell lung cancer.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/*blood/diagnosis/pathology ; Diagnosis, Differential ; Female ; Humans ; Lung Diseases/*blood ; Lung Neoplasms/*blood/diagnosis/pathology ; Male ; Middle Aged ; Peptide Fragments/*blood ; Recombinant Proteins/blood ; Sensitivity and Specificity ; Small Cell Lung Carcinoma/*blood/diagnosis/pathology ; Tumor Markers, Biological/*blood

OBJECTIVETo explore the diagnostic value of carcinoembryonic antigen (CEA) and cytokeratin-19-fragment (CYFRA21-1) in lung cancer patients.

METHODSThe levels of serum CEA and CYFRA21-1 were measured in 102 patients with lung cancer, 45 patients with benign lung disease and 36 health controls by electrochemiluminescence.

RESULTSThe level of serum CEA and positive rate [(25.77 ± 15.34) ng/ml, 47.1%] were significantly higher in the lung cancer group than that in the benign lung disease group [(4.67 ± 2.21) ml, 7.7%; P < 0.05] and controls [(3.98 ± 3.00) ng/ml, 3.8%; P < 0.05], The level of serum CYFRA21-1 and positive rate [(14.08 ± 8.34) ng/ml, 62.7%] were also significantly higher in the lung cancer group than that in the benign lung disease group [(3.27 ± 2.87) ml, 7.7%; P < 0.05] and controls [(2.69 ± 2.02 ng/ml, 3.8%; P < 0.05]. The difference of level of CEA and CYFRA21-1 between the benign lung disease group and controls was statistically not significant (P > 0.05). Both tumor markers were increased to a different degree in the lung cancer patients at various TNM stages [(CEA: stage II (17.78 ± 8.71) ng/ml, stage III (25.84 ± 7.34) ng/ml, stage IV (34.85 ± 6.99) ng/ml; and CYFRA21-1: stage II (10.05 ± 6.76) ng/ml, stage III (15.93 ± 6.66) ng/ml, stage IV (22.78 ± 4.12) ng/ml]. Combined use of both makers showed a significant higher sensitivity (77.5% vs. 47.1%, 62.8%), but reduced specificity (86.8% vs. 94.0%, 95.6%), and not significantly changed accuracy (83.5% vs. 77.1%, 83.8%) in the diagnosis of lung cancer.

CONCLUSIONSCEA and CYFRA21-1 employed separately are helpful in the diagnosis of lung cancer. Combined detection of these two tumor markers can improve the positivity for diagnosis of lung cancer.

Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; pathology ; Case-Control Studies ; Female ; Humans ; Keratin-19 ; blood ; Lung Diseases, Obstructive ; blood ; Lung Neoplasms ; blood ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonia ; blood ; Small Cell Lung Carcinoma ; blood ; diagnosis ; pathology ; Tuberculosis, Pulmonary ; blood

Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (beta hCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. beta hCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for beta hCG. Serum beta hCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, beta hCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. beta hCG expression may be associated with aggressive clinical course and increased risk of recurrence, also beta hCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma.
Brain Neoplasms/radiotherapy/secondary ; Carcinoma, Non-Small-Cell Lung/complications/*diagnosis/pathology ; Chorionic Gonadotropin, beta Subunit, Human/*blood ; Gynecomastia/*etiology ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Lymph Nodes/surgery ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Tomography, X-Ray Computed

OBJECTIVE: To investigate the relation between multi-slice spiral CT pulmonary perfusion imaging and the cavity of microvessel in lung cancer. METHODS: Altogether 36 patients with malignant nodules who underwent multi-slice spiral CT perfusion scan were examined.The perfusion parameters were collected and compared with the microvessel density (MVD), the incomplete lumen MVD, and the differentiation of non-small cell lung cancer (NSCLC). The patients were divided into a hyper-perfusion group and a hypo-perfusion group by the value of perfusion parameters. The maturity of microvessel and the degree of differentiation in NSCLC between the 2 groups was analyzed. RESULTS: Blood flow (BF), blood volume (BV), and peak enhancement image(PEI) of the malignant nodules were (39.7±11.5) mL/(100 mg.min), (8.6±3.8)mL/100 g, and (20.1±8.6)HU, respectively. There was a positive correlation between PEI and MVD(r=0.645,P<0.01), and a negative correlation between BF and MVD(r=-0.280,P=0.048). There were negative correlations of BF, BV, PEI with the incomplete lumen MVD (P<0.05). BF had the highest correlation coefficient(r=-0.882,P<0.01).The incomplete lumen MVD of the hyper-perfusion group was significantly lower than that of hypo-perfusion group (P<0.05),but there was no significant difference in MVD between the 2 groups. There were negative correlations of BF, BV,PEI with the degree of differentiation (P<0.05). BF had the highest correlation coefficient(r=-0.751,P<0.01). CONCLUSION Multi-slice spiral CT pulmonary perfusion imaging is helpful to evaluate the degree of differentiation and status of angiogenesis in lung cancer, and its basis is the cavity of microvessel.
Capillaries ; pathology ; Carcinoma, Non-Small-Cell Lung ; blood supply ; diagnostic imaging ; pathology ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms ; blood supply ; diagnostic imaging ; pathology ; Male ; Neovascularization, Pathologic ; diagnostic imaging ; Solitary Pulmonary Nodule ; blood supply ; diagnostic imaging ; pathology ; Tomography, Spiral Computed ; methods