Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to iden...Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.展开更多
Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstratin...Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking S1X1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs＆GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.展开更多
文摘Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.
文摘Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking S1X1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs＆GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.
