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ABSTRACT: Zinc finger protein, X-linked (ZFX) is a transcription factor encoded by its gene on the mammalian X chromosome, and functions to control survival and activity of stem cells and lymphocytes. However, little is known about the role of ZFX in tumorigenesis. The function of ZFX in cell proliferation was investigated by the lentivirus-mediated short hairpin RNA interference (shRNA) approach in non-small cell lung cancer (NSCLC) cell culture lines. The expression profiles of ZFX in 49 pairs of tumors and corresponding matched adjacent normal tissues from NSCLC patients were examined by real-time PCR. The specific knockdown of ZFX by shRNA significantly inhibited cell viability and reduced colony formation of 95D cells. And ZFX silencing resulted in cell cycle arrest in G0/G1 phase. In addition, ZFX was overexpressed and correlated with lymph node metastasis in samples from 49 NSCLC patients. We reported for the first time that ZFX may play an important role in cell growth control and cell cycle progression of 95D cells. Furthermore, ZFX was overexpressed in samples of NSCLC and ZFX mRNA expression associated with lymph node metastasis. Therefore, our findings suggest that ZFX would be a potential target to development of therapies for NSCLC.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2012; 20(4):171-8. · 1.30 Impact Factor
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ABSTRACT: To detect the expression of mammalian target of rapamycin (mTOR) and PTEN in non-small cell lung cancer (NSCLC), and explore their role in the prognosis of patients with NSCLC.
Samples of cancer tissues and normal lung tissues from 78 patients with NSCLC were examined for expression of mTOR and PTEN by real-time polymerase chain reaction and immunohistochemistry. The differences in mTOR and PTEN expression were compared by Student's t test. A Cox regression model was used to analyze the relationship between the influencing factors and the prognosis. Kaplan-Meier survival curves and the log-rank test were used to analyze the progression-free survival.
The mTOR expression in NSCLC tissues was significantly higher than that in normal lung tissue, while the levels of PTEN expression in NSCLC tissue were significantly lower than that in normal lung tissues (P < 0.05). No significant correlations were observed between the mTOR and PTEN expressions and the patients' age, sex, pathological type, differentiation, lymph node metastasis, or distant metastasis. The only correlation was with the T stage. The Cox regression analysis showed that mTOR and PTEN expression had an important impact on the patient prognosis.
The absence of and/or a low expression of PTEN and activated mTOR may play an important role in the development of NSCLC, and may represent new prognostic biomarkers for a poor prognosis in patients with NSCLC.
Surgery Today 11/2011; 42(5):419-25. · 1.22 Impact Factor
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Wentao Yue,
Xiaoting Zhao,
Lina Zhang, Shaofa Xu,
Zhidong Liu,
Li Ma,
Wenyun Jia,
Zhe Qian,
Chunyan Zhang,
Yue Wang,
Xuehui Yang
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ABSTRACT: The role of cell cycle protein cyclin Y (CCNY) in non-small-cell lung cancer (NSCLC) is not clear. Hence, the aim of this study was to explore the potential role of CCNY in lung cancer.
Real-time quantitative polymerase chain reaction was used for detecting the expression of CCNY mRNA in 60 samples from patients with NSCLC. The functional role of CCNY in NSCLC cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analysis of cell proliferation, anchorage-independent growth, and xenograft growth.
CCNY mRNA is overexpressed (N = 60) in samples from patients with NSCLC. Furthermore, CCNY mRNA expression positively correlated with histologic types (squamous cell carcinoma vs. adenocarcinomas; P = .048) and with the tumor size (size > 3 cm vs. size ≤ 3 cm; P = .010) in NSCLC. Functionally, CCNY depletion was shown to inhibit cell proliferation and anchorage-independent growth in lung cancer cells. Moreover, the proliferation effects were increased when CCNY was overexpressed in lung cancer cells. Finally, CCNY was shown to support H1299 and 95D xenograft growth in nude mice.
We reported for the first time (to the best of our knowledge) that CCNY was overexpressed in samples of NSCLC. CCNY mRNA expression associated with histologic types of NSCLC and promoted the malignant growth of lung cancer cell line in vivo and in vitro. Thus, these results validated the role of CCNY as a clinically relevant human oncoprotein and warrant further investigation of CCNY as a biomarker and a therapeutic target in NSCLC.
Clinical Lung Cancer 01/2011; 12(1):43-50. · 2.94 Impact Factor
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ABSTRACT: IL-8 (interleukin-8) has been identified as a chemotactic factor, but recent found that IL-8 and matrix metalloproteinase-9 (MMP-9) are important cytokines which are closely related to the growth and metastasis of tumor. The aim of this study is to explore the relationship between IL-8, MMP-9 expressions and clinical pathological features of non-small cell lung cancer (NSCLC) patients and evaluate the diagnostic potential of IL-8, MMP-9 as tumor markers.
The serum levels of IL-8 and MMP-9 were detected by enzyme-linked immunosorbentassay (ELISA) in 141 NSCLC patients, 40 healthy adults and 40 patients with benign pulmonary disease. The expressions of IL-8 and MMP-9 were detected by immunohistochemical method in 95 NSCLC tissues, and 21 benign disease lung tissues, 25 normal lung tissues as control.
The level of expression of IL-8 and MMP-9 in serum and tissue of NSCLC was significantly higher than that of healthy and benign respiratory disease, and the expression was gradually increased with the upgrade of clinicopathological stage. The serum and tissue expression of IL-8 and MMP-9 in NSCLC patients with lymph node metastasis was remarkably higher than that without lymph node metastasis. There is an positive correlation (r=0.765) between IL-8 and MMP-9 in the tissue of NSCLC patients.
This study has confirmed that IL-8, MMP-9 expressions are related to the development of NSCLC. There is an obvious correlation between IL-8 expression and lymph node metastasis, IL-8 may facilitate the lymph node metastasis by up-regulating MMP-9 expression. Serum level of IL-8 is a valuable auxiliary parameter in diagnosing lymph node metastases of NSCLC with good sensitivity and specificity.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 08/2010; 13(8):795-802.
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ABSTRACT: Autoantibodies as new tumor markers may play an important role in the early diagnosis and evaluating the prognosis of lung cancer. In this study, we detect epidermal growth factor receptor (EGFR) autoantibodies using peptide array and screen the epitopes which are recognized by EGFR autoantibodies.
Peptide array covering the extracellular domain of EGFR protein was synthesized by a synthesizer (ASPSL) made by Intavis company. EGFR autoantibodies in the serums of non-small cell lung cancer patients was detected using peptide array.
Six of 20 patients were found to have EGFR autoantibodies. The positive rate is 30%. Nine high frequency spots were found in the 6 positive patients and 8 high frequency spots clustered in the III and IV domains.
These findings will offer new clues for the further studies of EGFR and EGFR autoantibodies.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 07/2010; 13(7):727-30.
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ABSTRACT: It has been proved that mTOR was an important signal transduction molecular and protein kinase regulating cell growth and proliferation, and mTOR could activate the downstream protein effector. PTEN could negatively regulate mTOR signal pathway and inhibit its activity. The aim of this study is to detect the mRNA expression levels of mTOR and PTEN gene, which are the key genes of mTOR signaling pathway in human non-small cell lung cancer (NSCLC) tissue. The relationship between mTOR signaling pathway and NSCLC is also explored.
Lung cancer tissue specimens were obtained from 65 patients. Adjacent-tumor non-small cell lung cancer tissues from the 30 patients were served as control. The RT-PCR technique was used to detect the mTOR and PTEN gene expression levels.
The average mRNA expression levels of mTOR gene were significantly higher (0.23 +/- 0.16) in lung cancer than in adjacent-tumor tissue (0.12 +/- 0.09)(P < 0.01). The average mRNA expression levels of PTEN gene were (0.19 +/- 0.28) in lung cancer, while the mRNA expression levels of PTEN gene were (0.53 +/- 0.28) in adjacent-tumor tissue (P < 0.01). The levels of PTEN gene expression in non-small cell lung cancer were significantly lower than that in adjacent-tumor lung tissue. There are not significant relationship between mTOR and PTEN gene expression levels and patients' age, gender, pathological type, differentiation, lymph node metastasis, except tumor size.
The expression of mTOR is activated in NSCLC. The expression of PTEN is absent or decreased. The mTOR activated in NSCLC may be correlate with the absent or decreased of PTEN. The absent or decreased expression of PTEN and the actived mTOR may play important roles in carcinogenesis and metastasis of NSCLC.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 07/2010; 13(7):717-21.
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ABSTRACT: Adenoid cystic carcinoma is primary bronchopulmonary carcinoma with low malignancy, and 43 patients treated in the past 50 years in our hospital were retrospectively studied. The aim of this study is to discuss the clinical symptoms, pathologic characteristic and therapeutic method of primary tracheal or bronchuotracheal adenoid cystic carcinoma.
This study summarized total 43 patients of primary tracheal or bronchus adenoid cystic carcinoma treated in our hospital from Jan. 1958 to Dec. 2007. Among them, 40 patients were treated by surgical resection, and 3 patients were treated by fiberoptic bronchoscope's interventional treatment.
The 1-yr, 3-yr, 5-yr survival rates of the 43 patients above were 100% (41/41), 89.5% (34/38), 87.1% (27/31), respectively.
Primary tracheal or bronchus adenoid cystic carcinoma are rare and low malignancy carcinoma. The clinical symptoms of them are not typical. The best treatment is early detection and taking measures of operation plus radiotherapy. The other palliative treatment is fiberoptic bronchoscope's interventional treatment.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 06/2010; 13(6):628-31.
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WenTao Yue,
XiaoTing Zhao,
LiNa Zhang,
ZhiDong Liu,
Li Ma,
WenYun Jia,
Zhe Qian,
ChunYan Zhang,
Yue Wang,
XueHui Yang, ShaoFa Xu
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ABSTRACT: Cyclin Y (CCNY) is a key cell cycle regulator that acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery. The expression status of CCNY in lung cancer and its clinical significance remain unknown. The data indicates that CCNY may be deregulated in non-small cell lung cancer, where it may act to promote cell proliferation. These studies suggest that CCNY may be a candidate biomarker of NSCLC and a possible therapeutic target for lung cancer treatment.
Science China. Life sciences 04/2010; 53(4):511-6. · 2.02 Impact Factor
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Zhongguo fei ai za zhi = Chinese journal of lung cancer 01/2010; 13(1):69-72.
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Zhongguo fei ai za zhi = Chinese journal of lung cancer 10/2009; 12(10):1115-8.
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ABSTRACT: Serum autoantibody detection is useful means for the early diagnosis and prognosis of cancer. So our objective was to synthesize peptide array to analyse p53 autoantibodies in the sera of patients with non small cell lung cancer (NSCLC).
Cellulose-bound overlapping peptides (12 mers) derived from p53 wild type protein were synthesized using SOPTs synthesis technique by an AutoSpot robot -ASP SL (Intavis, Germany). The membrane was incubated with 1/400 dilutions of p53 monoclonal antibody (Sc-53394) to establish a new approach to detect p53 antibody, and the epitopes of the p53 monoclonal antibody is already known. We analysed the p53 autoantibodies from the sera of NSCLC and controls by peptide array and ELISA.
We synthesized on cellulose membranes twelve-amino-acid overlapping peptides which included all of the sequences of the polypeptide chain of p53. The p53 autoantibody was positive in seven cases of thirty patients sera with NSCLC and was negative in sera of the controls, with the same result of ELISA CONCLUSIONS: The peptide array could be applied not only to detect the autoantibodies in the sera of patients with lung cancer, but also to map the epitopes of the autoantibodies which might be useful for the early diagnosis and prognosis of cancer.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 09/2009; 12(9):969-74.
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ABSTRACT: As invasion and metastasis of cancer seriously threaten human's life, it is of more important clinical significance to understand and evaluate the biologic behavior of cancer correctly. Abnormal expression of integrin and ECM proteins play an important role in invasion and metastasis of cancer. The objective of this study is to analyze the expression of the integrin alpha5, beta1 and ECM proteins in patients with NSCLC and its correlation with lymph node (LN) metastasis as well as prognosis, and to evaluate its roles in the metastasis of tumor.
The expression of integrin alpha5, beta1 and collagen type IV, fibronectin, tenascin was determined by immunohistochemistry. The relationship was analysized that between integrin alpha5, beta1 and ECM proteins expression and clinico-pathologic parameters especially LN metastasis and prognosis.
The expression of collagen type IV was negatively correlated with LN metastasis, and positively to prognosis of patients; The expression of integrin alpha5, beta1 was positively correlated with LN metastasis, and integrin alpha5 was negatively to prognosis of patients. The expression of integrin alpha5 was positively correlated with the expression of integrin beta1, and negatively with the expression of collagen type IV. The expression of collagen type IV in stage I disease P-TNM stage was remarkably higher than that in stage III disease and poordifferentiated disease (P <0.001), but integrin alpha5, beta1 was significantly higher than that in stage III disease and poordifferentiated disease.
Increased expression of integrin alpha5, beta1 and decreased expression of ECM significantly correlated with LN metastasis of NSCLC. Integrin alpha5 and collagen type IV are prognosic factors in patients with NSCLC.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 05/2009; 12(5):397-402.
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ABSTRACT: Progress has been made in research of lung cancer tumor markers in recent years,and these tumor markers have been used in clinical application. This study is to evaluate the regimens of six serum tumor markers in lung cancer diagnosis.
The serum levels of the six tumor markers(NSE, pro-GRP, CYFRA21-1, SCC, p53 antibody and CA199) were detected in 80 healthy adults,170 patients with lung cancer and 80 patients with respiratory infection by ELISA.
The levels of the six tumor markers in patients with lung cancer were remarkably higher than those in healthy adults and patients with respiratory infection(P <0.01).The levels of the NSE,pro-GRP in patients with small cell lung cancer were significantly higher than those in other subtypes of the lung cancer(P <0.01);The levels of the CYFRA21-1,SCC in patients with squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P <0.01).The sensitivity of the NSE,pro-GRP in diagnosing small cell lung cancer was remarkably higher than that in other subtypes of the lung cancer(P <0.01); The sensitivity of the CYFRA21-1, SCC in diagnosing squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P <0.01).The sensitivity of the tumor markers combinations in diagnosing lung cancer was remarkably higher than that of the single marker (P <0.01).
Detection of the six tumor markers is helpful for diagnosis lung cancer. Combination of NSE and pro-GRP is more economic than other combinations in diagnosing small cell lung cancer; Combined CYFRA21-1,SCC is more economic than other combinations in diagnosing squamous carcinoma.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 04/2008; 11(2):256-9.
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ABSTRACT: With the development of social industrialization and aging of the population, patients with lung cancer have the tendency of becoming youthful and elderly, therefore the way of treatment should be also changed. In resent years, lung cancer in young and elderly patients have been reported respectively, but simultaneous contrast analysis of clinical feature and prognosis in elderly, normal and youthful patients have been rarely reported. Based on the clinic data in the patients, the clinical feature and prognosis of patients with non-small cell lung cancer at different ages were analyzed.
From January 1996 to January 2003, 1380 patients with NSCLC were treated surgically in thoracic department in our hospital, the patients were divided into three group based on their age, group 1 (G1) (range ≤40), group 2 (G2) (range 41-69), group 3 (G3) (range ≥70). The clinical feature and prognosis were analyzed in each group.
The mean age in the whole group was 58.16±0.26, and 35.76±0.57 (range 12-40) in G1, 58.00±0.22 (range 41-69) in G2, 72.30±0.21 (range 70-80) in G3. The ratio of lung cancer in female between G1 and G3 was significant different (P=0.024). The coexisting diseases in G3 were more common than those of other groups (P=0.000). Squamous cell carcinoma was the main type in histology, accounting for 41.79% (28/67), 54.12% (644/1190) and 58.54% (72/123) in each group respectively (P=0.080), but the ratio of adenocarcinoma, higher than that of other groups, were 43.28% (29/67), 29.50% (351/1190) and 26.82% (33/123) (P=0.036). Lobectomy and pneumonectomy were the main surgical procedures, accounting for 58.21%, 65.29%, 78.86% (P=0.004) and 34.33%, 26.22%, 12.20% (P=0.001), respectively. The ratio of stage III were 43.28% (29/67), 38.82% (462/1190), and 26.02% (32/123) in each groups (P=0.015). 55.22% (37/67) in G1 received adjuvant chemotherapy, 47.48% (565/1190) in G2, and 29.27% (36/123) in G3 (P=0.000). 5-year survival rate was 38.96% in the whole group, 29.99% in G1, 39.61% in G2, and 37.99% in G3 (P=0.494).
In young patients with non-small cell lung cancer, female and adenocarcinoma make up the majority of the number, and a lot of patients are in advanced stage and likely to adopt adjuvant chemotherapy. While in elderly, squamous cell carcinoma accounts for the majority of the number, and more coexisting diseases are accompanied, much more complications occur after surgical procedure. Nevertheless, their prognosis has no significant difference.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 10/2007; 10(5):418-21.
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ABSTRACT: Hepatoma-derived growth factor (HDGF), a novel growth factor, has a widely expression in many normal cells and tumor cells. It plays an important role in cell proliferation, differentiation and angiogenesis. It is considered as a promising marker for predicting the invasion, matastasis and prognosis of carcinomas in clinical researches. The aim of this study is to evaluate the expression of HDGF and its clinical implication in patients who undergone complete resection for stage I non-small cell lung cancer (NSCLC).
Immunohistochemical technology was applied to detect the expression of HDGF in 118 lung cancer tissues and 30 normal lung tissues as control.
HDGF staining was observed in nuclear as well as in cytoplasm. HDGF positively staining was seen in all patients, and remarkably higher than that in normal lung tissues (52.23±10.35 vs 156.73±70.95, P < 0.01). Expresson of HDGF was closely related to histological classification, but not to other clinicopathological factors, and the expression of HDGF in adenocarcinoma was much stronger than that in squamous cancers (P=0.001). Univariate analysis and multivariate Cox regression analysis showed that the patients with high HDGF expression had a shorter overall survival and HDGF was a significantly independent predictive factor for patients with stage I NSCLC (RR=1.011, P=0.002).
HDGF may be a promising predictive factor for stage I NSCLC, and the assessment of HDGF may provide new insight on carcinogenesis and development of stage I NSCLC .
Zhongguo fei ai za zhi = Chinese journal of lung cancer 08/2007; 10(4):291-5.
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ABSTRACT: The latest studies have demonstrated that postoperative adjuvant chemotherapy may improve survival in patients with stage I non-small cell lung cancer (NSCLC), so it was a challenge for clinician to choose the patients who might benefit from adjuvant chemotherapy. The aim of this study is to evaluate the prognostic implications of angiogenesis and tumor blood vessel invasion (BVI) in stage I NSCLC patients who underwent complete resection.
One hundred and eighteen stage I NSCLC patients undergoing complete resection from 1994-2002 were retrospectively reviewed. Angiogenesis was assessed by vascular endothelial growth factor (VEGF) and microvessel density (MVD), BVI was assessed by examining the direct invasion of tumor cells marked by CD34 within vessel lumen.
Low VEGF expression was seen in 44 patients (37.3%), high VEGF expression was in 74 patients (62.7%). The MVD of high VEGF expression cases was much higher than that of low VEGF expression ones (33.4±17.8 vs 24.7±14.8, P=0.010). There was a positive correlation between VEGF and MVD (r=0.216, P=0.019). The 5-year survival rate in patients with high VEGF expression was much lower than in those with low VEGF expression (36.48% vs 72.20%, P=0.003). The BVI was present in 32 patients (27.1%) and absent in 86 patients (72.9%). The 5-year survival rate in patients with presence of BVI was much lower than those with absence of BVI (34.38% vs 60.47%, P=0.018). Multivariate COX regression analysis showed that high VEGF expression and BVI were significantly independent predictive factors for overall survival. Finally, the presence of both risk factors, BVI and high VEGF expression was highly predictive of poor outcome (P= 0.001 ).
Tumor vessel invasion and high VEGF expression are independent prognostic factors for overall survival of postoperative stage I NSCLC. The assessment of these factors may improve prognostic stratification for adjuvant therapy or a targeted and specific treatment in stage I NSCLC.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 02/2007; 10(1):29-33.
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ABSTRACT: There are many factors that affect the prognosis of non-small cell lung cancer (NSCLC). This study aims to analyze the influential factors and prognosis in patients with NSCLC following operation.
From January 1996 to January 2003, 1380 patients with NSCLC treated surgically were retrospectively studied. The correlation between clinicopathological characteristics and prognosis was evaluated by univariate and multivariate analyses.
In the whole group, 1-, 3- and 5-year survival rate was 78.85%, 49.78% and 38.96% respectively, and median survival time (MST) was 38.77 months. According to univariate analysis, tumor size, pathologic type, clinical type (central or peripheral), TNM stages, lymph node involvement, surgical procedure, postoperative chemotherapy, and cycles of chemotherapy were significantly related to the survival of patients. By multivariate analysis, tumor size, TNM stages, lymph node status and postoperative chemotherapy were independent prognostic factors.
Tumor size, TNM stages, lymph node involvement and postoperative chemotherapy are independent prognostic factors for NSCLC following the surgical procedure.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 10/2006; 9(5):465-8.
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ABSTRACT: The influence of tumor size on prognosis has been determined in different stages of lung cancer, but it is not clear yet within the same stage of lung cancer, especially for those less than 3cm in diameter. The aim of this study is to explore the impact of tumor size on prognosis in stage IA non-small cell lung cancer (NSCLC).
A total of 142 consecutive, surgically treated patients with pathologic stage IA NSCLC were analysed retrospectively. Kaplan-Meier survival curve was performed to estimate the survival of patients with different tumor size. And a COX proportional hazard regression model was used to make multivariate analysis about age, gender, pathologic type, tumor size and chemoradiotherapy or not.
There were 60 patients with tumor diameter less than 2.0cm, and 82 between 2.1 to 3.0cm. The overall 3-and 5-year survival rate was 84.41% and 70.89% respectively, in which tumor diameter less than 2.0cm group was 94.91% and 81.40%, tumor diameter between 2.1 to 3.0cm group was 82.18% and 64.91% (P=0.0353), respectively. In both univariate and multivariate analyses, the tumor size was an independent prognostic factor for survival.
Since the tumor size is an independent prognostic factor for NSCLC, it is necessary to improve the level of imageological diagnosis so as to treat the patients much earlier.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 02/2006; 9(1):68-70.
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ABSTRACT: To summarize the operative indication, surgical technique and perioperative ma-nagement of resection and reconstruction of carina for advanced lung cancer involving the carina.
There were 67 patients with lung cancer invaded the carina, right central lung cancer in 46 cases, peripheral lung cancer in 4 cases, involved superior vena cava (SVC) or with bilateral anonymous veins in 11 cases, left central lung cancer in 17 cases, respectively. Surgical procedure included carinal right pneumonectomy or lobectomy in 50 cases, concomitant replacement of SVC or with bilateral anonymous veins with vascular prosthesis in 11 cases, carinal left pneumonectomy in 17 cases. Follow-up was performed in long-term.
Perioperative death occured in 8 cases (11.94%), circulatory failure in 6 cases (8.96%), and respiratory failure in 2 cases (2.99%). The overall 1-, 3- and 5-survival rate was 77.21%, 48.23% and 32.54% respectively.
Complete resection and reconstruction of carina, SVC or bilateral anonymous veins combined with postoperatively multiple modality therapy can get good prognosis for the patients with advanced lung cancer.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 10/2004; 7(5):434-7.
