Analyzing epidermal growth factor receptor mutation status changes in advanced non-small-cell lung cancer at different sampling time-points of blood within one day.

BACKGROUND: We investigated whether different sampling time-points within one day would influence epidermal growth factor receptor mutation (EGFRm) status in plasma and evaluated the clinical outcomes according to the quantity analysis of EGFRm in circulating tumor DNA (ctDNA) in non-small-cell lung cancer (NSCLC). METHODS: EGFR-tyrosine kinase inhibitor naïve advanced NSCLC patients who carried EGFRm in both tissues and ctDNA were enrolled in this study. Plasma samples were collected at three time-points within one day (at 8 am, 11 am and 2 pm) for EGFRm analysis by droplet digital PCR. RESULTS: Twenty-two advanced NSCLC patients were enrolled in the study. In a total of 66 blood specimens, the median EGFRm frequency was 7.13% (range 0-35.09%), and among them six specimens had less than 1.0% EGFRm frequency. Moreover, one time-point blood specimen did not display any EGFRm, even by droplet digital PCR. The frequency of EGFRm changed dynamically across different time-points within one day, but the differences were not significant (P = 0.557). We observed that patients with a relatively high frequency of EGFRm (>6.76%) had a better response to gefitinib (P = 0.024). CONCLUSION: The release of ctDNA maybe a temporal heterogenous process. The different sampling time-points within one day did not seem to influence EGFRm status in ctDNA. The relative EGFRm frequency in ctDNA could predict a benefit of EGFR-tyrosine kinase inhibitor treatment for advanced NSCLC patients.

Expression and clinical significance of matrix metalloproteinase (MMP)-26 protein in non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinase (MMP)-26 has been implicated in genesis, progression, invasion and metastasis of several types of human cancers. This study was to investigate the expression of MMP-26 protein in invasive non-small cell lung cancer (NSCLC), pre-invasive lung cancer and normal lung tissues, thus to explore the role of MMP-26 in the progression and prognosis of NSCLC. METHODS: SP immunohistochemistry was used to measure the expression of MMP-26 protein in 72 specimens of NSCLC, 14 specimens of atypical hyperplasia and 10 specimens of normal lung tissues. RESULTS: The high expression rate of MMP-26 was 0 (0/10) in normal lung tissues, 14.3% (2/14) in atypical hyperplasia and 59.7% (43/72) in NSCLC. The expression rate of MMP-26 protein was significantly higher in NSCLC than in atypical hyperplasia and normal lung tissues (p < 0.01); the expression was higher in atypical hyperplasia than in normal lung tissues, but the difference was not significant (p > 0.05). The high expression rate of MMP-26 protein was significantly correlated to stage (p < 0.05) and lymph node metastasis (p < 0.05), but not to age, gender, tumor size and differentiation (p > 0.05). Multivariate analysis showed that MMP-26 and stage were independent prognostic factors of NSCLC (p < 0.05). The disease-free survival and overall survival were shorter in NSCLC patients with high expression of MMP-26 than in those with low expression of MMP-26 (log-rank = 19.34 and 23.2, both p < 0.001). CONCLUSIONS: High expression of MMP-26 protein is correlated to carcinogenesis, lymph node metastasis, clinical stage and prognosis of NSCLC. Therefore, MMP-26 may be served as a tumor marker in monitoring progression and predicting prognosis of NSCLC.

[The expression of vascular endothelial growth factor, CD44v6 in non-small cell lung carcinoma].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF), CD44v6 in non-small cell lung carcinoma. METHODS: The expression of VEGF and CD44v6 in 35 cases I approximately II stages, 27 cases III approximately IV stages and 50 cases with the metastasis of lymph nodes, 12 cases without metastasis of non-small cell lung carcinoma (NSCLC) tissues were studied by SP immunohistochemistry staining, and the 3 years survival rates were calculated in 42 cases patients. RESULTS: The positive rates of VEGF and CD44v6 in NSCLC were 73% and 69%, respectively. They were both higher than those of matched normal lung tissues, P < 0.01. The expression of VEGF and CD44v6 were related to clinical stages and metastasis of lymph nodes significantly. The expression rates of the two markers in NSCLC with the metastasis of lymph nodes were higher than those without metastasis, chi(2) = 7.146 and 5.376 respectively, and those of III approximately IV stages were higher than those of I approximately II Stages, chi(2) = 6.392 and 12.152 respectively. Survival rates of three years were lower to those patients with positive expression of the two makers than those with negative expression. In a multivariate analysis, besides TNM stages and metastasis of lymph nodes, the positive expression of CD44v6 and the positive expression of VEGF were also the independent prognostic factors to affect the Survival time. CONCLUSION: The VEGF and CD44v6 protein may act as one of important indexes to indicate the process of infiltration and metastasis in NSCLC.