目的:通过多肽组学分析研究多肽在肺腺癌发生发展中的作用及潜在分子机制。方法:提取3对年龄匹配的男性肺腺癌组织和癌旁组织的内源性多肽,通过液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)筛选差异...目的:通过多肽组学分析研究多肽在肺腺癌发生发展中的作用及潜在分子机制。方法:提取3对年龄匹配的男性肺腺癌组织和癌旁组织的内源性多肽,通过液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)筛选差异表达的多肽,借助生物信息学推测差异多肽的潜在功能,使用CCK-8实验、划痕实验、Transwell实验验证重点多肽对肺腺癌细胞株(A549、H1975)恶性表型的影响。结果:鉴定了10 kDa以下的多肽4 538条,共筛选出242条在癌组织和癌旁组织间存在差异表达的多肽(差异倍数≥2.0,FDR<0.05),对应202个前体蛋白。GO分析以及KEGG通路富集分析的结果显示这些蛋白与肿瘤发生发展的一系列重要生物学活动密切相关。聚焦于首次发现的多肽LACRP2,体外实验证实该多肽可以一定程度上抑制肺腺癌细胞株的恶性表型。结论:内源性多肽LACRP2可能与肺腺癌部分恶性表型有关。多肽组学可以更全面地帮助了解肺腺癌的发生发展机制。展开更多
Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs （miRNAs）.We investigated the role of miR-503 in the development of cisplatin resist...Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs （miRNAs）.We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.Methods MiR-503 expression was measured by quantitative real-time PCR.MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of miR-503.Immunohistochemistry,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.Results MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines.Additionally,downregulation of miR-503 in the cisplatin （DDP）-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor （IGF1R） and B-cell lymphoma 2 （BCL2） expression compared with the parental SGC7901 cell line.An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin.The luciferase activity of reporters driven by IGF1R and BCL2 3＇-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503.Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced apoptosis.Conclusion Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.展开更多
Background We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio （the ratio between metastatic lymph nodes and total dissected lymph nodes,MLNR） in patients with gastri...Background We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio （the ratio between metastatic lymph nodes and total dissected lymph nodes,MLNR） in patients with gastric adenocaminoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric cancer.Methods From January 2005 to December 2010,1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were included.In particular,lymph node metastasis was not present in 515 patients.The number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease outcome.The survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier plots.Results The overall 5-year survival rate was 54％ in this group.Univariate analysis revealed that age category,macroscopic appearance,histological grade,tumor size,depth of primary tumor invasion,number of metastatic lymph nodes,metastatic lymph nodes ratio,tumor,nodes,metastasis-classification （TNM） stage and status of lymphovascular,and vessel invasion have significant impact on survival.The number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival （P ＜0.001）.However,in multivariate analyses,only the metastatic lymph nodes ratio was identified to be an independent prognostic factor （P ＜0.001）.The number of removed lymph nodes in node-negative was a strong prognostic factor of survival,the more lymph nodes dissected,the better the survival.Conclusions The metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph nodes.The number of removed lymph nodes miaht be an important proanostic factor for gastric cancer without lymph node metastasis.展开更多
基金This research was supported by grants from the National Natural Science Foundation of China （No.81201705 and No.81201796） and the Natural Science Foundation of Jiangsu Province （No.BK2012442）.
文摘Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs （miRNAs）.We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.Methods MiR-503 expression was measured by quantitative real-time PCR.MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of miR-503.Immunohistochemistry,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.Results MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines.Additionally,downregulation of miR-503 in the cisplatin （DDP）-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor （IGF1R） and B-cell lymphoma 2 （BCL2） expression compared with the parental SGC7901 cell line.An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin.The luciferase activity of reporters driven by IGF1R and BCL2 3＇-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503.Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced apoptosis.Conclusion Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.
文摘Background We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio （the ratio between metastatic lymph nodes and total dissected lymph nodes,MLNR） in patients with gastric adenocaminoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric cancer.Methods From January 2005 to December 2010,1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were included.In particular,lymph node metastasis was not present in 515 patients.The number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease outcome.The survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier plots.Results The overall 5-year survival rate was 54％ in this group.Univariate analysis revealed that age category,macroscopic appearance,histological grade,tumor size,depth of primary tumor invasion,number of metastatic lymph nodes,metastatic lymph nodes ratio,tumor,nodes,metastasis-classification （TNM） stage and status of lymphovascular,and vessel invasion have significant impact on survival.The number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival （P ＜0.001）.However,in multivariate analyses,only the metastatic lymph nodes ratio was identified to be an independent prognostic factor （P ＜0.001）.The number of removed lymph nodes in node-negative was a strong prognostic factor of survival,the more lymph nodes dissected,the better the survival.Conclusions The metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph nodes.The number of removed lymph nodes miaht be an important proanostic factor for gastric cancer without lymph node metastasis.
