- 作者列表："Li N","Zeng Y","Huang J
BACKGROUND:An increasing number of studies have focused on the early diagnostic value of the methylation of RASSF1A and SHOX2 in lung cancer. However, the intricate cellular events related to RASSF1A and SHOX2 in lung cancer are still a mystery. For researchers and clinicians aiming to more profoundly understand the diagnostic value of methylated RASSF1A and SHOX2 in lung cancer, this review will provide deeper insights into the molecular events of RASSF1A and SHOX2 in lung cancer. METHODOLOGY:We searched for relevant publications in the PubMed and Google Scholar databases using the keywords "RASSF1A", "SHOX2" and "lung cancer" etc. First, we reviewed the RASSF1A and SHOX2 genes, from their family structures to the functions of their basic structural domains. Then we mainly focused on the roles of RASSF1A and SHOX2 in lung cancer, especially on their molecular events in recent decades. Finally, we compared the value of measuring RASSF1A and SHOX2 gene methylation with that of the common methods for the diagnosis of lung cancer patients. RESULTS:The RASSF1A and SHOX2 genes were confirmed to be regulators or effectors of multiple cancer signaling pathways, driving tumorigenesis and lung cancer progression. The detection of RASSF1A and SHOX2 gene methylation has higher sensitivity and specificity than other commonly used methods for diagnosing lung cancer, especially in the early stage. CONCLUSIONS:The RASSF1A and SHOX2 genes are critical for the processes of tumorigenesis, development, metastasis, drug resistance, and recurrence in lung cancer. The combined detection of RASSF1A and SHOX2 gene methylation was identified as an excellent method for the screening and surveillance of lung cancer that exhibits high sensitivity and specificity.
背景: 越来越多的研究集中于RASSF1A和SHOX2 甲基化在肺癌中的早期诊断价值。然而，肺癌中与RASSF1A和SHOX2 相关的错综复杂的细胞事件仍然是个谜。对于旨在更深刻理解甲基化RASSF1A和SHOX2 在肺癌中的诊断价值的研究人员和临床医生来说，本综述将为RASSF1A和SHOX2 在肺癌中的分子事件提供更深入的见解。 方法: 我们使用关键词 “RASSF1A” 、 “SHOX2” 和 “肺癌” 等在PubMed和Google Scholar数据库中搜索相关出版物。首先，我们回顾了RASSF1A和SHOX2 基因，从其家族结构到其基本结构域的功能。然后我们主要关注RASSF1A和SHOX2 在肺癌中的作用，特别是近几十年来它们的分子事件。最后，我们比较了检测RASSF1A和SHOX2 基因甲基化与常用方法对肺癌患者诊断的价值。 结果: 证实RASSF1A和SHOX2 基因是多个癌症信号通路的调节因子或效应物，驱动肿瘤发生和肺癌进展。RASSF1A和SHOX2 基因甲基化的检测比其他常用的诊断肺癌的方法具有更高的敏感性和特异性，特别是在早期阶段。 结论: RASSF1A和SHOX2 基因在肺癌的发生、发展、转移、耐药和复发过程中起关键作用。联合检测RASSF1A和SHOX2 基因甲基化被认为是筛查和监测肺癌的极好方法，具有很高的灵敏度和特异性。
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.