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Increased expression of TTC21A in lung adenocarcinoma infers favorable prognosis and high immune infiltrating level.

TTC21A在肺腺癌中的表达增加预示着良好的预后和高免疫浸润水平。

  • 影响因子:3.32
  • DOI:10.1016/j.intimp.2019.106077
  • 作者列表:"Wang W","Ren S","Wang Z","Zhang C","Huang J
  • 发表时间:2020-01-01
Abstract

BACKGROUND:Lung adenocarcinoma (LUAD) is a crucial pathological type of lung cancer. Immune-infiltration of the tumor microenvironment positively associated with overall survival in LUAD. TTC21A is a gene has not reported in cancer, and the mechanism behind it is still unclear. Our study assesses TTC21A role in LUAD, via TCGA data. METHODS:GEPIA was utilized to analyze the expression of TTC21A in LUAD. We evaluated the influence of TTC21A on survival of LUAD patients by survival module. Then, data sets of LUAD were downloaded from TCGA. The correlations between clinical information and TTC21A expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression. In addition, we explored the correlation between TTC21A and cancer immune infiltrates using CIBERSORT and "Correlation" module of GEPIA. RESULTS:The univariate analysis using logistic regression, wherein TTC21A expression served as a categorical dependent variable (with a median expression value of 2.5), indicated that increased TTC21A expression is significantly correlated with pathological stage, tumor status and lymph nodes. Moreover, multivariate analysis revealed that the up-regulated TTC21A expression, negative results of pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, a positive correlation between increased TTC21A expression and immune infiltrating level of B cells, Neutrophils, Mast cells and T cells was established using CIBERSORT analysis. Furthermore, we confirmed it in "correlation" module of GEPIA. CONCLUSION:Together with all these findings, increased TTC21A expression correlates with favorable prognosis and increased proportion of immune cells, such as B cells, Neutrophils, Mast cells and T cells in LUAD. These conclusions indicate that TTC21A could serve as a potential biomarker to assess prognosis and immune infiltration level in LUAD.

摘要

背景: 肺腺癌 (LUAD) 是肺癌的重要病理类型。LUAD中肿瘤微环境的免疫浸润与总生存期正相关。TTC21A是癌症中尚未报道的基因,其背后的机制尚不清楚。我们的研究通过TCGA数据评估TTC21A在LUAD中的作用。 方法: 利用GEPIA分析TTC21A在LUAD中的表达。我们通过生存模块评估了TTC21A对LUAD患者生存的影响。然后,从TCGA下载LUAD的数据集。使用logistic回归分析临床信息与TTC21A表达之间的相关性。使用Cox回归与TCGA患者总生存期相关的临床病理特征。此外,我们使用CIBERSORT和GEPIA的 “相关性” 模块探讨了TTC21A与癌症免疫浸润之间的相关性。 结果: 使用logistic回归的单因素分析,其中TTC21A表达作为分类因变量 (表达中值为 2.5),表明TTC21A表达增加与病理分期显著相关,肿瘤状态和淋巴结。多因素分析显示,TTC21A表达上调、病理分期阴性和远处转移是预后良好的独立预后因素。具体而言,使用CIBERSORT分析建立了TTC21A表达增加与b细胞、嗜中性粒细胞、肥大细胞和T细胞的免疫浸润水平之间的正相关。此外,我们在GEPIA的 “相关” 模块中证实了它。 结论: 在LUAD中,TTC21A表达增加与预后良好和免疫细胞比例增加有关,如b细胞、中性粒细胞、肥大细胞和T细胞。这些结论表明TTC21A可以作为评估LUAD预后和免疫浸润水平的潜在生物标志物。

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影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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