Clinicopathologic Features and the Prognostic Implications of Long Noncoding RNA HOTAIRM1 in Non-Small Cell Lung Cancer.
长链非编码RNA HOTAIRM1 在非小细胞肺癌中的临床病理特征和预后意义。
- 作者列表："Xiong F","Yin H","Zhang H","Zhu C","Zhang B","Chen S","Ling C","Chen X
: Aims: The purpose of this study was to explore the value of long noncoding RNA-HOXA transcript antisense RNA myeloid-specific 1 (LncRNA-HOTAIRM1) as a prognostic candidate for detecting non-small cell lung cancer (NSCLC). Materials and Methods: The cancer cell line encyclopedia online database was utilized to analyze HOTAIRM1 expression in different tumor cell lines and to estimate the relationship between HOTAIRM1 and clinicopathologic parameters based on the chi-square test. We compared the LncRNA-HOTAIRM1 levels in cancerous and paracancerous tissues of NSCLC patients using quantitative real-time polymerase chain reaction assays. The Kaplan-Meier method was performed to analyze overall survival (OS). Results: LncRNA-HOTAIRM1 showed varied expression levels in different malignant tumor cell lines. There was a significant association between the expression of HOTAIRM1 and histopathological differentiation, tumor size, tumor/node/metastasis (TNM) stage, and Ki-67 of NSCLC patients. In addition, the relative expression of HOTAIRM1 in NSCLC tissues was significantly higher when compared with the individual patients' matched paracancerous tissues. Patients in the group with low expression levels of HOTAIRM1 had a longer OS than those in the group with high expression levels for lung adenocarcinoma, I-II stages of NSCLC, and NSCLC with smoking history. Conclusion: Our study suggests that LncRNA-HOTAIRM1 is highly expressed in NSCLC, and is associated with a poor prognosis, higher clinicopathologic grade, and smoking. LncRNA-HOTAIRM1 is a potential diagnostic and prognostic biomarker for NSCLCs.
: 目的: 本研究的目的是探讨长链非编码RNA-HOXA转录反义RNA髓样特异性 1 (LncRNA-HOTAIRM1) 的价值作为检测非小细胞肺癌 (NSCLC) 的预后候选者。 材料与方法: 利用癌症细胞系百科全书在线数据库分析HOTAIRM1 在不同肿瘤细胞系中的表达，并基于卡方检验估计HOTAIRM1 与临床病理参数之间的关系。我们使用定量实时聚合酶链反应试验比较了NSCLC患者癌组织和癌旁组织中的LncRNA-HOTAIRM1 水平。采用Kaplan-Meier法分析总生存期 (OS)。 结果: LncRNA-HOTAIRM1 在不同的恶性肿瘤细胞系中显示出不同的表达水平。HOTAIRM1 的表达与NSCLC患者的组织病理学分化程度、肿瘤大小、肿瘤/淋巴结/转移 (TNM) 分期以及Ki-67 的NSCLC患者之间存在显著相关性。此外，与个体患者匹配的癌旁组织相比，HOTAIRM1 在NSCLC组织中的相对表达显著更高。HOTAIRM1 低表达组的患者比肺腺癌、NSCLC i-ii期和有吸烟史的NSCLC高表达组的患者具有更长的OS。 结论: 我们的研究表明，LncRNA-HOTAIRM1 在NSCLC中高表达，并与预后差、临床病理分级高和吸烟相关。LncRNA-HOTAIRM1 是nsclc的潜在诊断和预后生物标志物。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
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.
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.